tbuckley/cabot-search huggingface dataset:
Serologic Immunity to Diphtheria and Tetanus in the United States
Authors: Geraldine M. McQuillan, Deanna Kruszon-Moran, Adamadia Deforest, Susan Y. Chu, Melinda Wharton
Journal: Annals of Internal Medicine (2002)

Background: Serologic data on diseases that are preventable by vaccine are useful to evaluate the success of immunization programs and to identify susceptible subgroups. Objective: To provide national estimates of immunity to diphtheria and tetanus by measurement of serum antibody levels. Design: Examination of data from the Third National Health and Nutrition Examination Survey, a representative cross-sectional sample of the U.S. population. Setting: 89 randomly selected locations throughout the United States. Participants: 18 045 persons 6 years of age or older who were examined from 1988 to 1994. Measurements: Serum samples obtained at a single time point were tested for diphtheria and tetanus antitoxin. Results: Overall, 60.5% of Americans 6 years of age or older had fully protective levels of diphtheria antibody (≥ 0.10 IU/mL) and 72.3% had protective levels of tetanus antibody (>0.15 IU/mL). Ninety-one percent of Americans 6 to 11 years of age had protective levels of both diphtheria and tetanus antibody; this proportion decreased to approximately 30% among persons 70 years of age (29.5% for diphtheria and 31.0% for tetanus). Adult Mexican-Americans were slightly less likely to have protective levels of antibody to both toxins. Only 47% of persons 20 years of age or older had levels that were protective against both diseases, and only 63% of adults who were protected against tetanus were also protected against diphtheria. Conclusions: A substantial proportion of adults in the United States do not have antibody levels that are protective against diphtheria and tetanus. In addition, although the recommended vaccine is a combination of tetanus and diphtheria, only 63% of adults with protective antibody to tetanus also had protective antibody to diphtheria.
Chronic viral hepatitis in children: any role for the pathologist?
Authors: M. Guido, F. Bortolotti
Journal: Gut (2008)

> The child is father of the man (William Wordsworth)

Among human hepatitis viruses, hepatitis B (HBV) and C (HCV) are able to persist in the host for years and principally contribute to the establishment of chronic hepatitis. A large number of people, worldwide, is still estimated to be infected with HBV and HCV: 370 and 130 million, respectively.1

In endemic areas, HBV infection is often acquired perinatally or early in childhood and becomes chronic in a high proportion of cases. Universal vaccination of newborns has been effective in reducing the spread of infection. However, hepatitis B is still a social–sanitary problem in undeveloped areas where immunisation policies are unavailable and in developed countries, where the reservoir of infection is maintained by immigration and adoption. In some endemic areas children with chronic hepatitis B are also at risk for superinfection with the hepatitis delta virus (HDV), which worsens the prognosis of liver disease.

In the absence of a specific vaccination, HCV infection remains a major global health problem. Although efficient therapies are now available, HCV-related end-stage liver disease is still the most frequent indication for liver transplantation in adult patients. The spread of HCV infection in childhood is much more limited,2 3 but vertical transmission, though of low efficiency, contributes to maintaining the reservoir of infection worldwide.4 Based on a projection model for paediatric HCV outcomes, it has been suggested that HCV infection will have a significant economic impact over the next 10 years.5

Indeed, chronic viral hepatitis acquired in childhood is a long-lasting process based on host–virus interactions, which may change over the years. A number of factors related to the virus (genotype, therapy), to the host (hormonal status, immunocompetence, therapy) and to the environment (alcohol, drugs, co-infections) can interfere with the natural history of the …
Inflammatory dendritic cells—not basophils—are necessary and sufficient for induction of Th2 immunity to inhaled house dust mite allergen
Authors: Hamida Hammad, Maud Plantinga, Kim Deswarte, Philippe Pouliot, Monique A.M. Willart, Mirjam Kool, Femke Muskens, Bart N. Lambrecht
Journal: The Journal of Experimental Medicine (2010)

It is unclear how Th2 immunity is induced in response to allergens like house dust mite (HDM). Here, we show that HDM inhalation leads to the TLR4/MyD88-dependent recruitment of IL-4 competent basophils and eosinophils, and of inflammatory DCs to the draining mediastinal nodes. Depletion of basophils only partially reduced Th2 immunity, and depletion of eosinophils had no effect on the Th2 response. Basophils did not take up inhaled antigen, present it to T cells, or express antigen presentation machinery, whereas a population of FceRI(+) DCs readily did. Inflammatory DCs were necessary and sufficient for induction of Th2 immunity and features of asthma, whereas basophils were not required. We favor a model whereby DCs initiate and basophils amplify Th2 immunity to HDM allergen.
Celecoxib induces hepatic stellate cell apoptosis through inhibition of Akt activation and suppresses hepatic fibrosis in rats
Authors: Y-H Paik, J K Kim, J I Lee, S H Kang, D Y Kim, S H An, S J Lee, D K Lee, K-H Han, C Y Chon, S I Lee, K S Lee, D A Brenner
Journal: Gut (2009)

<h3>Background and aims:</h3> Activated hepatic stellate cells (HSCs) but not quiescent HSCs express cyclo-oxygenase-2 (COX-2), suggesting that the COX-2/prostanoid pathway has an active role in hepatic fibrogenesis. However, the role of COX-2 inhibitors in hepatic fibrogenesis remains controversial. The aim of this study was to investigate the antifibrotic effects of celecoxib, a selective COX-2 inhibitor. <h3>Methods:</h3> The effects of various COX inhibitors—that is, ibuprofen, celecoxib, NS-398 and DFU, were investigated in activated human HSCs. Then, the antifibrotic effect of celecoxib was evaluated in hepatic fibrosis developed by bile duct ligation (BDL) or peritoneal thioacetamide (TAA) injection in rats. <h3>Results:</h3> Celecoxib, NS-398 and DFU inhibited platelet-derived growth facor (PDGF)-induced HSC proliferation; however, only celecoxib (⩾50 μM) induced HSC apoptosis. All COX inhibitors completely inhibited prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) and PGI<sub>2</sub> production in HSCs. Separately, PGE<sub>2</sub> and PGI<sub>2</sub> induced cell proliferation and extracellular signal-regulated kinase (ERK) activation in HSCs. All COX inhibitors attenuated ERK activation, but only celecoxib significantly inhibited Akt activation in HSCs. Celecoxib-induced apoptosis was significantly attenuated in HSCs infected with adenovirus containing a constitutive active form of Akt (Ad5myrAkt). Celecoxib had no significant effect on PPARγ (peroxisome proliferator-activated receptor γ) expression in HSCs. Celecoxib inhibited type I collagen mRNA and protein production in HSCs. Oral administration of celecoxib (20 mg/kg/day) significantly decreased hepatic collagen deposition and α-SMA (α-smooth muscle actin) expression in BDL- and TAA-treated rats. Celecoxib treatment significantly decreased mRNA expression of COX-2, α-SMA, transforming growth factor β1 (TGFβ1) and collagen α1(I) in both models. <h3>Conclusions:</h3> Celecoxib shows a proapoptotic effect on HSCs through Akt inactivation and shows antifibrogenic effects in BDL- and TAA-treated rats, suggesting celecoxib as a novel antifibrotic agent of hepatic fibrosis.
Validation of a Gene Expression Signature for Assessment of Lymph Node Metastasis in Oral Squamous Cell Carcinoma
Authors: Sander R. van Hooff, Frank K.J. Leusink, Paul Roepman, Robert J. Baatenburg de Jong, Ernst-Jan M. Speel, Michiel W.M. van den Brekel, Marie-Louise F. van Velthuysen, Paul J. van Diest, Robert J.J. van Es, Matthias A.W. Merkx, J. Alain Kummer, C. René Leemans, Ed Schuuring, Johannes A. Langendijk, Martin Lacko, Maria J. De Herdt, Jeroen C. Jansen, Ruud H. Brakenhoff, Piet J. Slootweg, Robert P. Takes, Frank C.P. Holstege
Journal: Journal of Clinical Oncology (2012)

Current assessment of lymph node metastasis in patients with head and neck squamous cell carcinoma is not accurate enough to prevent overtreatment. The aim of this study was validation of a gene expression signature for distinguishing metastasizing (N+) from nonmetastasizing (N0) squamous cell carcinoma of the oral cavity (OSCC) and oropharynx (OPSCC) in a large multicenter cohort, using a diagnostic DNA microarray in a Clinical Laboratory Improvement Amendments/International Organization for Standardization-approved laboratory.A multigene signature, previously reported as predictive for the presence of lymph node metastases in OSCC and OPSCC, was first re-evaluated and trained on 94 samples using generic, whole-genome, DNA microarrays. Signature genes were then transferred to a dedicated diagnostic microarray using the same technology platform. Additional samples (n=222) were collected from all head and neck oncologic centers in the Netherlands and analyzed with the diagnostic microarray. Human papillomavirus status was determined by real-time quantitative polymerase chain reaction.The negative predictive value (NPV) of the diagnostic signature on the entire validation cohort (n=222) was 72%. The signature performed well on the most relevant subset of early-stage (cT1-T2N0) OSCC (n=101), with an NPV of 89%.Combining current clinical assessment with the expression signature would decrease the rate of undetected nodal metastases from 28% to 11% in early-stage OSCC. This should be sufficient to enable clinicians to refrain from elective neck treatment. A new clinical decision model that incorporates the expression signature is therefore proposed for testing in a prospective study, which could substantially improve treatment for this group of patients.
Letter in response to 'Coagulation and fibrosis in chronic liver disease'
Authors: K Borensztajn, M P Peppelenbosch, C A Spek
Journal: Gut (2009)

We read with interest the paper by Calvaruso and colleagues discussing the role of coagulation in fibrosis in chronic liver disease.1 Fibrotic diseases, and especially liver fibrosis, are a major public health issue, and remain too often refractory to therapy. Novel treatment options are therefore eagerly awaited. Overall, we agree with the author’s conclusions that compelling evidence supports a close relationship between thrombin and hepatic fibrogenesis and that targeting the coagulation cascade might be an attractive therapeutic avenue for the management of liver fibrosis. This notion is underscored by the fact that anticoagulant therapy already showed promise in idiopathic pulmonary fibrosis where it improved overall survival.2

Although we would …
A Population-Based Study of Hepatitis D Virus as Potential Risk Factor for Hepatocellular Carcinoma
Authors: J. Ji, K. Sundquist, J. Sundquist
Journal: JNCI Journal of the National Cancer Institute (2012)

Hepatitis D virus (HDV) is dependent on the presence of hepatitis B virus (HBV) for transmission and replication because of its inability to produce its own coat. It remains unclear whether HDV infection increases the risk of hepatocellular carcinoma. Using the Swedish Hospital Discharge Register and Outpatient Registry, we identified 9160 patients with chronic HBV infection between 1997 and 2008, of whom 327 had chronic HDV infection and 323 had acute HDV infection. Standardized incidence ratios (SIRs) were calculated for these patients compared with the general population. The risk of hepatocellular carcinoma was greatly increased in patients with HBV and HDV (SIR = 137.17, 95% confidence interval [CI] = 62.19 to 261.51). The risk of hepatocellular carcinoma among patients with HBV and HDV was increased (SIR = 6.11, 95% CI = 2.77 to 11.65) when patients with chronic HBV infection alone were used as the reference population. Similar results were observed for patients with chronic HDV infection (SIR = 99.26, 95% CI = 42.39 to 196.55). Our findings indicate that HDV is a strong risk factor for hepatocellular carcinoma.
Rate Dependent Aberrancy
Authors: CHARLES FISCH, DOUGLAS P. ZIPES, PAUL L. McHENRY
Journal: Circulation (1973)

Forty patients with "rate dependent aberrancy" (RDA) were studied. This large group of patients permitted a clear definition of the syndrome and recognition of a number of features not previously described. These proved to have a significant bearing on the recognition and differential diagnosis of RDA and non-rate dependent aberrancy. It was found that a small change in cycle length, perhaps too small to be recognized in the surface ECG, can result in RDA. Consequently, if a critical shortening of cycle length is to be recognized, it is necessary to record not only the onset of aberrant rhythm but also sufficiently long strips with normal intraventricular conduction preceding and following the RDA. In some patients there was no recognizable sudden change in cycle length and the onset of aberrancy was a function of the duration of the accelerated rate. In others only the first cycle of the rhythm with RDA was shortened and the remaining R-R intervals were paradoxically longer than the R-R cycle which initiated the RDA. The aberrancy in RDA occurred at relatively slow heart rates (in 26 of the 40 patients the rate was below 80), and was frequently independent of any significant changes in the duration of the immediately preceding cycle length. There was a striking prevalence of left bundle branch block, and in 35 of the 40 patients obvious organic heart disease was documented.
The Effects of Opioids and Opioid Analogs on Animal and Human Endocrine Systems
Authors: Cassidy Vuong, Stan H. M. Van Uum, Laura E. O'Dell, Kabirullah Lutfy, Theodore C. Friedman
Journal: Endocrine Reviews (2009)

Opioid abuse has increased in the last decade, primarily as a result of increased access to prescription opioids. Physicians are also increasingly administering opioid analgesics for noncancer chronic pain. Thus, knowledge of the long-term consequences of opioid use/abuse has important implications for fully evaluating the clinical usefulness of opioid medications. Many studies have examined the effect of opioids on the endocrine system; however, a systematic review of the endocrine actions of opioids in both humans and animals has, to our knowledge, not been published since 1984. Thus, we reviewed the literature on the effect of opioids on the endocrine system. We included both acute and chronic effects of opioids, with the majority of the studies done on the acute effects although chronic effects are more physiologically relevant. In humans and laboratory animals, opioids generally increase GH and prolactin and decrease LH, testosterone, estradiol, and oxytocin. In humans, opioids increase TSH, whereas in rodents, TSH is decreased. In both rodents and humans, the reports of effects of opioids on arginine vasopressin and ACTH are conflicting. Opioids act preferentially at different receptor sites leading to stimulatory or inhibitory effects on hormone release. Increasing opioid abuse primarily leads to hypogonadism but may also affect the secretion of other pituitary hormones. The potential consequences of hypogonadism include decreased libido and erectile dysfunction in men, oligomenorrhea or amenorrhea in women, and bone loss or infertility in both sexes. Opioids may increase or decrease food intake, depending on the type of opioid and the duration of action. Additionally, opioids may act through the sympathetic nervous system to cause hyperglycemia and impaired insulin secretion. In this review, recent information regarding endocrine disorders among opioid abusers is presented.
Somatic Hypermutation Shapes the Antibody Repertoire of Memory B Cells in Humans
Authors: Eric Meffre, Nadia Catalan, Françoise Seltz, Alain Fischer, Michel C. Nussenzweig, Anne Durandy
Journal: The Journal of Experimental Medicine (2001)

High-affinity antibodies produced by memory B cells differ from antibodies produced in naive B cells in two respects. First, many of these antibodies show somatic hypermutation, and second, the repertoire of antibodies expressed in memory responses is highly selected. To determine whether somatic hypermutation is responsible for the shift in the antibody repertoire during affinity maturation, we analyzed the immunoglobulin lambda light chain (Igλ) repertoire expressed by naive and antigen-selected memory B cells in humans. We found that the Igλ repertoire differs between naive and memory B cells and that this shift in the repertoire does not occur in the absence of somatic hypermutation in patients lacking activation-induced cytidine deaminase (AID). Our work suggests that somatic hypermutation makes a significant contribution to shaping the antigen-selected antibody repertoire in humans.
The Chloroplast Genomes of the Green Algae Pedinomonas minor, Parachlorella kessleri, and Oocystis solitaria Reveal a Shared Ancestry between the Pedinomonadales and Chlorellales
Authors: M. Turmel, C. Otis, C. Lemieux
Journal: Molecular Biology and Evolution (2009)

The green algae belonging to the Chlorophyta—the lineage sister to that comprising the land plants and their charophycean green algal relatives (Streptophyta)—have been subdivided into four classes (Prasinophyceae, Ulvophyceae, Trebouxiophyceae, and Chlorophyceae). Yet the Pedinomonadales, an assemblage consisting of tiny, naked uniflagellates with a second basal body, has no clear affiliation with these classes and the branching order of the crown chlorophytes remains unknown. To gain an insight into the phylogenetic position of the Pedinomonadales and the relationships among the recognized chlorophyte classes, we have sequenced the chloroplast genomes of Pedinomonas minor (Pedinomonadales) and of two trebouxiophyceans belonging to the Chlorellales, Parachlorella kessleri (Chlorellaceae) and Oocystis solitaria (Oocystaceae), and compared these genomes with those of previously examined streptophytes and chlorophytes, including Chlorella vulgaris (Chlorellaceae). Unlike their Chlorella homolog, the three newly investigated chloroplast DNAs (cpDNAs) carry a large rRNA-encoding inverted repeat (IR) that divides the genome into large and small single-copy regions. In contrast to the situation found for ulvophycean and chlorophycean cpDNAs, the gene contents of the IR and single-copy regions are strikingly similar to that inferred for the common ancestor of chlorophytes and streptophytes. The intronless 98,340-bp Pedinomonas genome is among the chlorophyte cpDNAs featuring the smallest size and most ancestral gene organization. All 105 conserved genes encoded by this genome are included in the gene repertoires of Oocystis (111 genes) and Chlorella (113 genes), with just trnR(ccg) missing from Parachlorella cpDNA. Trees inferred from 71 cpDNA-encoded genes/proteins of 16 chlorophytes and nine streptophytes showed that Pedinomonas is nested in the Chlorellales, a group of algae lacking flagella. This phylogenetic conclusion is independently supported by uniquely shared gene linkages. We hypothesize that chlorellalean and pedinomonadalean green algae are reduced forms of a distant biflagellate ancestor that might have also given rise to the other known trebouxiophycean lineages. Our structural cpDNA data suggest that the Chlorellales and Pedinomonadales represent a deep branch of core chlorophytes, strengthening the notion that the Trebouxiophyceae emerged before the Ulvophyceae and Chlorophyceae. Our results further emphasize the importance of secondary reduction at both the cellular and genome levels during chlorophyte evolution.
The natural history of the renal manifestations of systemic lupus erythematosus. 1964.
Authors: V E Pollak, C L Pirani, F D Schwartz
Journal: Journal of the American Society of Nephrology (1997)

Journal of the American Society of Nephrology : JASN 8(7):p 1189-1198, July 1997. | DOI: 10.1681/ASN.V871189
The composition of house dust mite is critical for mucosal barrier dysfunction and allergic sensitisation
Authors: S Post, M C Nawijn, T L Hackett, M Baranowska, R Gras, A J M van Oosterhout, I H Heijink
Journal: Thorax (2011)

<h3>Background</h3> House dust mite (HDM) allergens have been reported to increase airway epithelial permeability, thereby facilitating access of allergens and allergic sensitisation. <h3>Objectives</h3> The authors aimed to understand which biochemical properties of HDM are critical for epithelial immune and barrier responses as well as T helper 2-driven experimental asthma in vivo. <h3>Methods</h3> Three commercially available HDM extracts were analysed for endotoxin levels, protease and chitinase activities and effects on transepithelial resistance, junctional proteins and pro-inflammatory cytokine release in the bronchial epithelial cell line 16HBE and normal human bronchial cells. Furthermore, the effects on epithelial remodelling and airway inflammation were investigated in a mouse model. <h3>Results</h3> The different HDM extracts varied extensively in their biochemical properties and induced divergent responses in vitro and in vivo. Importantly, the Greer extract, with the lowest serine protease activity, induced the most pronounced effects on epithelial barrier function and CCL20 release in vitro. In vivo, this extract induced the most profound epithelial E-cadherin delocalisation and increase in CCL20, CCL17 and interleukin 5 levels, accompanied by the most pronounced induction of HDM-specific IgE, goblet cell hyperplasia, eosinophilic inflammation and airway hyper-reactivity. <h3>Conclusions</h3> This study shows the ability of HDM extracts to alter epithelial immune and barrier responses is related to allergic sensitisation but independent of serine/cysteine protease activity.
The evaluation of pulmonary rehabilitation on health status in COPD patients by CAT questionnaire
Authors: Tanja Pavlovic, Dejan Pavlovic, Dusica Celeketic, Vesna Mandic, Tijana Vidakovic
Journal: European Respiratory Journal (2013)

COPD symptoms cough, shortness of breath, wheezing, and chest tightness cause limited basic activity. The level of physical disability experienced by patients with COPD varies considerably. Pulmonary rehabilitation (PR) is recommended for patients with chronic lung diseases.   The aim of our study  was to evaluate the influence of pulmonary rehabilitation on health status in COPD patients by using CAT questionnaire.   METHODS  - We evaluated 30 patients with stable COPD, involved in Pulmonary Rehabilitation program, for a period of 6 months. Severity of airflow obstruction was assessed by standard spirometry and classified by the Global initiative for Obstructive Lung Disease (GOLD) criteria; functional capacity was evaluated by the 6-min walk distance (6MWD). The impact of COPD on health status was assessed using COPD Assessment Test (CAT). All measures were obtained at baseline and 6 month.   RESULTS  - The patients’ average age was 62 years (46-74). All the patients were categorized with moderate to severe COPD. Imapct level at initial CAT scor was medium and high. After 6 months of pulmonary rehabilitation lung function testing showed marginal improvement of vital capacity (+1±0.6%); 6MWD improved by 59±2 m (14%) and the mean CAT questionnaire demonstrated a reduction of the score for -2.4±5.1 units.   CONCLUSIONS  - Pulmonary rehabilitation is a highly effective and safe intervention that improves physical activity, health status and quality of life in COPD patients. The correlation of 6MWD and CAT score may point that CAT questionnaire in sensitive in the evaluation of PR.