tbuckley/cabot-search huggingface dataset:
Preparation, characterization, and immunogenicity of Haemophilus influenzae type b polysaccharide-protein conjugates.
Authors: R Schneerson, O Barrera, A Sutton, J B Robbins
Journal: The Journal of Experimental Medicine (1980)

A method is presented for covalently bonding Haemophilus influenzae type b capsular polysaccharide (HIB Ps) to several proteins. The method is efficient and relies upon the use of adipic dihydrazide as a spacer between the capsular polysaccharide and the carrier protein. In contrast to the poor immunogenicity of the purified HIB Ps in mice and rabbits, the HIB Ps-protein conjugates induced serum anti-type b antibodies having bactericidal activity at levels shown to be protective in humans when low doses were injected subcutaneously in a saline solution. The antibody response in mice was related to the dose of the conjugates, increased with the number of injections, and could be primed by the previous injection of the carrier protein. The HIB Ps-protein conjugates were immunogenic in three different mouse strains. The importance of the carrier molecule for the enhanced immunogenicity of the HIB Ps-protein conjugates was shown by the failure of HIB Ps hybrids prepared with either the homologous polysaccharide or pneumococcus type 3 polysaccharide to induce antibodie in mice. Rabbits injected with the HIB Ps-protein conjugates emulsified in Freund's adjuvant produced high levels of serum anti-type b antibodies which induced a bactericidal effect upon H. influenzae type b organisms. It is proposed that the HIB Ps component of the polysaccharide protein conjugates has been converted to a thymic-dependent immunogen. This method may be used to prepare protein-polysaccharide conjugates with HIB Ps and other polysaccharides to be considered for human use.
Definition of Primary and Secondary Glioblastoma—Response
Authors: Hiroko Ohgaki, Peter Burger, Paul Kleihues
Journal: Clinical Cancer Research (2014)

We thank Dr. Barthel and colleagues for taking an interest in our review on primary and secondary glioblastoma (1). They present the case of a 72-year-old patient with an IDH1 mutation–negative glioblastoma, monitored by combined [11C]methionine (MET) amino acid transport PET/MRI. They diagnosed the first tumor as a low-grade astrocytoma, based on the absence of contrast enhancement in MRI, and unremarkable nuclear magnetic resonance (NMR) spectroscopy, but without histologic confirmation. Only 6 weeks later, a typical contrast-enhancing mass on MRI with further increase in amino acid transport was shown. Resection and histopathologic examination revealed a glioblastoma. The very short clinical history, absence of an IDH1 mutation, and the evidence of EGFR overexpression and LOH at the PTEN locus on chromosome 10, strongly support the diagnosis of a primary glioblastoma. This most common glioblastoma type is typically defined by a lack of clinical, radiologic, or histologic evidence of a less malignant precursor lesion. Their evolution is so fast that early lesions almost always escape clinical detection. The case presented by Dr. Barthel and colleagues is an exceptional observation as it shows a small precursor lesion shortly before the diagnosis of a large glioblastoma. We present a similar observation (Fig. 1; ref. 2). Following a seizure attack, the MRI of the 79-year-old patient showed a small cortical lesion that within 10 weeks developed into a full-blown glioblastoma with perifocal edema and central necrosis. For neither of these cases do we postulate that the precursor lesion was a low-grade astrocytoma. Instead, we got a rare glimpse of the remarkable dynamics of the evolution of primary glioblastomas.See the original Letter to the Editor, p. 2011No potential conflicts of interest were disclosed.
Helping people with severe mental illness to obtain work: systematic review
Authors: R. E Crowther
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objective:</b> To determine the most effective way of helping people with severe mental illness to obtain competitive employment—that is, a job paid at the market rate, and for which anyone can apply. <b>Design:</b> Systematic review. <b>Participants:</b> Eligible studies were randomised controlled trials comparing prevocational training or supported employment (for people with severe mental illness) with each other or with standard community care. <b>Outcome measures:</b> The primary outcome was number of subjects in competitive employment. Secondary outcomes were other employment outcomes, clinical outcomes, and costs. <b>Results:</b> Eleven trials met the inclusion criteria. Five (1204 subjects) compared prevocational training with standard community care, one (256 subjects) compared supported employment with standard community care, and five (484 subjects) compared supported employment with prevocational training. Subjects in supported employment were more likely to be in competitive employment than those who received prevocational training at 4, 6, 9, 12, 15, and 18 months (for example, 34% <i>v</i> 12% at 12 months; number needed to treat 4.45, 95% confidence interval 3.37 to 6.59). This effect was still present, although at a reduced level, after a sensitivity analysis that retained only the highest quality trials (31% <i>v</i> 12%; 5.3, 3.6 to 10.4). People in supported employment earned more and worked more hours per month than those who had had prevocational training. <b>Conclusion:</b> Supported employment is more effective than prevocational training at helping people with severe mental illness obtain competitive employment.
Methadone Versus Buprenorphine With Contingency Management or Performance Feedback for Cocaine and Opioid Dependence
Authors: Richard S Schottenfeld, Marek C Chawarski, Juliana R Pakes, Michael V Pantalon, Kathleen M Carroll, Thomas R Kosten
Journal: American Journal of Psychiatry (2005)

Physicians may prescribe buprenorphine for opioid agonist maintenance treatment outside of narcotic treatment programs, but treatment guidelines for patients with co-occurring cocaine and opioid dependence are not available. This study compares effects of buprenorphine and methadone and evaluates the efficacy of combining contingency management with maintenance treatment for patients with co-occurring cocaine and opioid dependence.Subjects with cocaine and opioid dependence (N=162) were provided manual-guided counseling and randomly assigned in a double-blind design to receive daily sublingual buprenorphine (12-16 mg) or methadone (65-85 mg p.o.) and to contingency management or performance feedback. Contingency management subjects received monetary vouchers for opioid- and cocaine-negative urine tests, which were conducted three times a week; voucher value escalated during the first 12 weeks for consecutive drug-free tests and was reduced to a nominal value in weeks 13-24. Performance feedback subjects received slips of paper indicating the urine test results. The primary outcome measures were the maximum number of consecutive weeks abstinent from illicit opioids and cocaine and the proportion of drug-free tests. Analytic models included two-by-two analysis of variance and mixed-model repeated-measures analysis of variance.Methadone-treated subjects remained in treatment significantly longer and achieved significantly longer periods of sustained abstinence and a greater proportion drug-free tests, compared with subjects who received buprenorphine. Subjects receiving contingency management achieved significantly longer periods of abstinence and a greater proportion drug-free tests during the period of escalating voucher value, compared with those who received performance feedback, but there were no significant differences between groups in these variables during the entire 24-week study.Methadone may be superior to buprenorphine for maintenance treatment of patients with co-occurring cocaine and opioid dependence. Combining methadone or buprenorphine with contingency management may improve treatment outcome.
Impaired cardiac autonomic control relates to disease severity in pulmonary hypertension
Authors: R. Wensel, C. Jilek, M. Dörr, D. P. Francis, H. Stadler, T. Lange, F. Blumberg, C. Opitz, M. Pfeifer, R. Ewert
Journal: European Respiratory Journal (2009)

Pulmonary arterial hypertension (PAH) results in chronic right heart failure, which is associated with an increase in sympathetic tone. This may adversely affect cardiac autonomic control. We investigated the changes in cardiac autonomic nervous activity in relation to disease severity in patients with PAH. In 48 patients with PAH (median World Health Organization class III, pulmonary artery pressure 52±14 mmHg, pulmonary vascular resistance 1,202±718 dyn·s·cm −5 , cardiac index 2.0±0.8 L·min −1 ·m −2 ) and 41 controls, cardiac autonomic nervous activity was evaluated by measurement of heart rate variability (HRV) and baroreflex sensitivity. All patients underwent cardiopulmonary exercise testing (peak oxygen uptake 13.2±5.1 mL·kg −1 ·min −1 , minute ventilation/carbon dioxide production slope 47±16). In patients with PAH, spectral power of HRV was reduced in the high-frequency (239±64 versus 563±167 ms 2 ), low-frequency (245±58 versus 599±219 ms 2 ) and very low-frequency bands (510±149 versus 1106±598 ms 2 ; all p&lt;0.05). Baroreflex sensitivity was also blunted (5.8±0.6 versus 13.9±1.2 ms·mmHg −1 ; p&lt;0.01). The reduction in high-frequency (r = 0.3, p = 0.04) and low-frequency (r = 0.33, p = 0.02) spectral power and baroreflex sensitivity (r = 0.46, p&lt;0.01) was related to the reduction in peak oxygen uptake. Patients with PAH have a marked alteration in cardiac autonomic control that is related to exercise capacity and may, therefore, serve as an additional marker of disease severity.
Vitamins E and C in the Prevention of Prostate and Total Cancer in Men
Authors: J. Michael Gaziano, Robert J. Glynn, William G. Christen, Tobias Kurth, Charlene Belanger, Jean MacFadyen, Vadim Bubes, JoAnn E. Manson, Howard D. Sesso, Julie E. Buring
Journal: JAMA (2008)

Many individuals take vitamins in the hopes of preventing chronic diseases such as cancer, and vitamins E and C are among the most common individual supplements. A large-scale randomized trial suggested that vitamin E may reduce risk of prostate cancer; however, few trials have been powered to address this relationship. No previous trial in men at usual risk has examined vitamin C alone in the prevention of cancer.To evaluate whether long-term vitamin E or C supplementation decreases risk of prostate and total cancer events among men.The Physicians' Health Study II is a randomized, double-blind, placebo-controlled factorial trial of vitamins E and C that began in 1997 and continued until its scheduled completion on August 31, 2007. A total of 14,641 male physicians in the United States initially aged 50 years or older, including 1307 men with a history of prior cancer at randomization, were enrolled.Individual supplements of 400 IU of vitamin E every other day and 500 mg of vitamin C daily.Prostate and total cancer.During a mean follow-up of 8.0 years, there were 1008 confirmed incident cases of prostate cancer and 1943 total cancers. Compared with placebo, vitamin E had no effect on the incidence of prostate cancer (active and placebo vitamin E groups, 9.1 and 9.5 events per 1000 person-years; hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.85-1.09; P = .58) or total cancer (active and placebo vitamin E groups, 17.8 and 17.3 cases per 1000 person-years; HR, 1.04; 95% CI, 0.95-1.13; P = .41). There was also no significant effect of vitamin C on total cancer (active and placebo vitamin C groups, 17.6 and 17.5 events per 1000 person-years; HR, 1.01; 95% CI, 0.92-1.10; P = .86) or prostate cancer (active and placebo vitamin C groups, 9.4 and 9.2 cases per 1000 person-years; HR, 1.02; 95% CI, 0.90-1.15; P = .80). Neither vitamin E nor vitamin C had a significant effect on colorectal, lung, or other site-specific cancers. Adjustment for adherence and exclusion of the first 4 or 6 years of follow-up did not alter the results. Stratification by various cancer risk factors demonstrated no significant modification of the effect of vitamin E on prostate cancer risk or either agent on total cancer risk.In this large, long-term trial of male physicians, neither vitamin E nor C supplementation reduced the risk of prostate or total cancer. These data provide no support for the use of these supplements for the prevention of cancer in middle-aged and older men.clinicaltrials.gov Identifier: NCT00270647.
Regulation of B-Cell Differentiation: Interactions of Factors and Corresponding Receptors
Authors: Toshiyuki Hamaoka, Shiro Ono
Journal: Annual Review of Immunology (1986)

The antibody response to nominal antigen such as hapten-carrier con­ jugates involves the cooperation of hapten-specific B cells and carrier­ specific helper T cells (1-4). In addition to the carrier specificity, helper T cells recognize determinants encoded by genes in the class-II major histocompatibility complex (MHC) on antigen-presenting cells as well as on B cells (5-13). The interaction between helper T cells and antigen­ presenting accessory cells (APC) is genetically restricted by products of the major histocompatibility complex (14-16). However, the cellular interac­ tions between helper T cells and B cells have been reported as restricted by self-MHC products (5-7, 10-12, 17) or not restricted by the MHC elements (18, 19). Since genetic restrictions imposed by products of the MHC are considered as a requirement for the recognition by T cells of self-MHC determinants expressed by non-T cells (APC), this controversy can be explained on the basis of whether T cells must necessarily recognize the MHC determinants expressed by B cells in order to trigger them to secrete antibodies. Since the original description of a role for T cells in the antigen­ dependent stimulation of B cells, a great deal of effort has gone toward elucidating the mechanism by which helper T cells function. A series of studies demonstrated that some members of the B-cell population participate in cognate cellular interactions with helper T cells. Cognate interaction refers to the recognition of both antigen and a class-II MHC molecule on the B-cell surface as a requirement for activation. Other
Adiponectin Trajectories Before Type 2 Diabetes Diagnosis
Authors: Adam G. Tabák, Maren Carstensen, Daniel R. Witte, Eric J. Brunner, Martin J. Shipley, Markus Jokela, Michael Roden, Mika Kivimäki, Christian Herder
Journal: Diabetes Care (2012)

The role of adiponectin in the natural history of diabetes is not well characterized. We set out to characterize prediagnosis trajectories of adiponectin in individuals who develop type 2 diabetes.In a case-cohort study (335 incident diabetes case and 2,474 noncase subjects) nested in the Whitehall II study, serum adiponectin was measured up to three times per participant (1991-1993, 1997-1999, and 2003-2004). Multilevel models adjusted for age and ethnicity were fitted to assess 13-year trajectories of log-transformed adiponectin preceding diabetes diagnosis or a randomly selected time point during follow-up (year(0)) based on 755/5,095 (case/noncase) person-examinations.Adiponectin levels were lower in diabetes case than in noncase subjects (median 7,141 [interquartile range 5,187-10,304] vs. 8,818 [6,535-12,369] ng/mL at baseline, P < 0.0001). Control subjects showed a modest decline in adiponectin throughout follow-up (0.3% per year, P < 0.0001) at higher levels in women than in men (difference at year(0): 5,358 ng/mL, P < 0.0001). Female case and early-onset case (age at diagnosis <52 years) subjects had a steeper decline than control subjects (slope difference -1.1% per year, P = 0.001 in females, -1.6% per year in early-onset case subjects, P = 0.034). In men, adiponectin slopes for case and noncase subjects were parallel. The slope differences by diabetes onset were largely attenuated after adjustment for changes in obesity, whereas the sex-specific slope differences were independent of obesity.Lower adiponectin levels were observed already a decade before the diagnosis of diabetes. The marked sex difference in trajectories suggests that sex-specific mechanisms affect the association between adiponectin levels and diabetes development.
Body-Surface Distribution of Changes in Activation-Recovery Intervals Before and After Catheter Ablation in Patients With Wolff-Parkinson-White Syndrome
Authors: Makoto Akahoshi, Makoto Hirai, Yasuya Inden, Hiroaki Sano, Atsuya Shimizu, Takahisa Kondo, Mitsutaka Makino, Mitsuru Horiba, Yukihiko Yoshida, Naoya Tsuboi, Haruo Hirayama, Teruo Ito, Hiroshi Hayashi, Hidehiko Saito
Journal: Circulation (1997)

Background T-wave abnormalities after catheter ablation in patients with manifest Wolff-Parkinson-White (WPW) syndrome have been attributed to a continuation of repolarization abnormalities induced by preexcitation (cardiac memory). Methods and Results To clarify changes in repolarization properties, we analyzed the activation-recovery interval (ARI) obtained from body-surface maps and the relationship between the activation time (AT) and ARI in 30 patients with WPW syndrome (group A, 18 patients with manifest left-sided accessory pathway; group B, 7 patients with manifest right-sided accessory pathway; and group C, 5 patients with concealed left-sided accessory pathway) before, 1 day after, and 1 week after ablation. The ARI significantly decreased 1 week after ablation compared with before and 1 day after ablation over the preexcited area in groups A and B. Correlation coefficients between the AT and ARI showed a significantly ( P &lt;.01) stronger inverse relationship before ( r =−.58) and 1 week after ( r =−.64) ablation than 1 day after ablation ( r =−.46) in groups A and B. In group C, the ARI and correlation coefficients between the AT and ARI showed no significant changes. Conclusions These findings suggest a prolongation of the action-potential duration over the preexcited area before and just after ablation as ventricular “electrical remodeling,” a decrease in the inverse relationship between the AT and action-potential duration 1 day after ablation, and a gradual recovery of the action-potential duration over the preexcited area and inverse relationship 1 week after ablation.
Incremental Benefit of Myocardial Contrast to Combined Dipyridamole-Exercise Stress Echocardiography for the Assessment of Coronary Artery Disease
Authors: Stuart Moir, Brian A. Haluska, Carly Jenkins, Robert Fathi, Thomas H. Marwick
Journal: Circulation (2004)

Although assessment of myocardial perfusion by myocardial contrast echocardiography (MCE) is feasible, its incremental benefit to stress echocardiography is not well defined. We examined whether the addition of MCE to combined dipyridamole-exercise echocardiography (DExE) provides incremental benefit for evaluation of coronary artery disease (CAD).MCE was combined with DExE in 85 patients, 70 of whom were undergoing quantitative coronary angiography and 15 patients with a low probability of CAD. MCE was acquired by low-mechanical-index imaging in 3 apical views after acquisition of standard resting and poststress images. Wall motion, left ventricular opacification, and MCE components of the study were interpreted sequentially, blinded to other data. Significant (>50%) stenoses were present in 43 patients and involved 69 coronary territories. The addition of qualitative MCE improved sensitivity for the detection of CAD (91% versus 74%, P=0.02) and accurate recognition of disease extent (87% versus 65% of territories, P=0.003), with a nonsignificant reduction in specificity.The addition of low-mechanical-index MCE to standard imaging during DExE improves detection of CAD and enables a more accurate determination of disease extent.
MAP kinase phosphatase 1 controls innate immune responses and suppresses endotoxic shock
Authors: Qun Zhao, Xianxi Wang, Leif D. Nelin, Yongxue Yao, Ranyia Matta, Mary E. Manson, Reshma S. Baliga, Xiaomei Meng, Charles V. Smith, John A. Bauer, Cheong-Hee Chang, Yusen Liu
Journal: The Journal of Experimental Medicine (2005)

Septic shock is a leading cause of morbidity and mortality. However, genetic factors predisposing to septic shock are not fully understood. Excessive production of proinflammatory cytokines, particularly tumor necrosis factor (TNF)-α, and the resultant severe hypotension play a central role in the pathophysiological process. Mitogen-activated protein (MAP) kinase cascades are crucial in the biosynthesis of proinflammatory cytokines. MAP kinase phosphatase (MKP)-1 is an archetypal member of the dual specificity protein phosphatase family that dephosphorylates MAP kinase. Thus, we hypothesize that knockout of the Mkp-1 gene results in prolonged MAP kinase activation, augmented cytokine production, and increased susceptibility to endotoxic shock. Here, we show that knockout of Mkp-1 substantially sensitizes mice to endotoxic shock induced by lipopolysaccharide (LPS) challenge. We demonstrate that upon LPS challenge, Mkp-1−/− cells exhibit prolonged p38 and c-Jun NH2-terminal kinase activation as well as enhanced TNF-α and interleukin (IL)-6 production compared with wild-type cells. After LPS challenge, Mkp-1 knockout mice produce dramatically more TNF-α, IL-6, and IL-10 than do wild-type mice. Consequently, Mkp-1 knockout mice develop severe hypotension and multiple organ failure, and exhibit a remarkable increase in mortality. Our studies demonstrate that MKP-1 is a pivotal feedback control regulator of the innate immune responses and plays a critical role in suppressing endotoxin shock.
Three cases of bronchial stump aspergillosis: unusual clinical presentations and beneficial effect of oral itraconazole
Authors: M Noppen, I Claes, B Maillet, M Meysman, I Monsieur, W Vincken
Journal: European Respiratory Journal (1995)

Bronchial stump aspergillosis (BSA), i.e. Aspergillus infection of bronchial granulation tissue surrounding endobronchial suture threads, is a very rare variant of localized suppurative bronchial Aspergillus infection. The majority of reported cases have occurred within one year after lung surgery. We present three more patients, in whom BSA occurred very late (4.5, 6 and 7 yrs) after pulmonary resection. Other unusual features were: complete absence of symptoms in one patient, and simultaneous occurrence of aspergilloma in another. Removal of the endobronchial suture probably constitutes the key therapy for BSA. In all three of our patients oral itraconazole resulted in clinical, histological and microbiological improvement. In conclusion, BSA should be considered in the differential diagnosis of haemoptysis occurring up to 7 yrs after lung surgery, although an asymptomatic presentation is possible. Furthermore, BSA can be associated with other clinical presentations of Aspergillus infection, e.g. aspergilloma. Finally, long-term oral itraconazole therapy may represent a valid alternative when removal of the suture is not feasible.