tbuckley/cabot-search huggingface dataset:
Guillain-Barré Syndrome in Heroin Addiction
Authors: W. Richard Smith
Journal: JAMA (1975)

In two cases of Guillain-Barré syndrome (acute polyneuritis) as a complication of narcotic abuse, the onset of paralysis began approximately 4 and 12 hours after self-administration of opiates intravenously. Bulbar and respiratory paralysis developed in one patient and required prolonged ventilation therapy; the other patient had peripheral muscular and unilateral facial weakness, with notable pleocytosis was present in both.
Glomerular and Renal Vascular Structural Changes in α8 Integrin-Deficient Mice
Authors: Christian S. Haas, Kerstin Amann, Johannes Schittny, Barbara Blaser, Ulrich Müller, Andrea Hartner
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Integrins are matrix receptors that regulate cell-matrix interactions during development and in adult tissue. In the adult kidney, the α8 chain is specifically expressed in glomerular mesangial cells and vascular smooth muscle cells. α8-deficient (α8−/−) mice demonstrate reductions in renal mass, which can range from complete renal agenesis to the development of kidneys that are only slightly smaller than wild-type kidneys. No histologic abnormalities of these kidneys have been described. However, considering the prominent expression of α8 in glomeruli and renal vessels, it seemed unlikely that the kidneys of α8−/− mice would be completely normal. Therefore, the renal phenotype of adult α8−/− mice was investigated, for assessment of more subtle morphologic alterations in kidney tissue. α8−/− mice displayed a significant reduction in nephron number and an increase in glomerular volume, compared with wild-type control animals. Albuminuria was not different in wild-type and α8−/− mice. Quantitative morphologic analyses revealed that the glomeruli of α8−/− mice were hypercellular, with an increased number of mesangial cells, compared with wild-type mice. Mesangial matrix deposition (as demonstrated for collagen IV and the α8 ligand fibronectin) was expanded in α8−/− mice, compared with wild-type mice. Collagens I and III, which are not normally present in glomeruli, were detected in the glomeruli of α8−/− mice. Staining for other glomerular integrins demonstrated an increased abundance of the collagen receptor α2 integrin in α8−/− mice. The glomerular capillary length density was significantly greater in α8−/− mice than in wild-type mice. Cortical arterial vessel walls were not altered in α8−/− mice, but the capillaries of the peritubular network were widened. Despite the strong mesangial and vascular expression of α8, glomerular and renal vascular alterations in α8−/− mice were relatively mild. Only aged α8−/− mice demonstrated increased glomerular capillary widening, compared with control animals. The results suggest that the lack of α8 can be largely compensated for, at least in younger α8−/− mice. It is not yet clear whether the occurrence of collagens that are not normally present in glomeruli and the increased abundance of the collagen receptor α2 contribute to maintaining the glomerular structure in α8−/− mice. The compensatory mechanisms involved will be the subject of future research. E-mail: Andrea.Hartner@rzmail.uni-erlangen.de
Phosphodiesterase 5 (PDE 5) inhibitors for the treatment of male erectile disorder: Attaining selectivity versus PDE6
Authors: Dmitri Pissarnitski
Journal: Medicinal Research Reviews (2005)

Abstract The role of phosphodiesterase type 5 (PDE5) in the mechanism of male erection has been well understood, and several drugs inhibiting this enzyme are being used for the treatment of erectile dysfunction (ED). Discovery of inhibitors with improved selectivity versus other PDE isozymes could lead to drugs with improved safety profile. Achievement of selectivity versus PDE6, co‐inhibition of which results in disturbances of color perception, remains the most challenging aspect of current drug discovery programs. The present review describes several case studies, where significant (&gt;100 fold) selectivity versus PDE6 has been attained via investigation of structure–activity relationships (SAR). Special attention is given to the chemical routes leading to novel chemotypes and allowing efficient exploration of their SAR's. Strategies for attaining inhibitor selectivity discussed below may be applicable for other drug discovery programs. © 2005 Wiley Periodicals, Inc. Med Res Rev
Biochemical predictors of pulmonary embolism
Authors: Adeel Ashraf, Arun Lakhanpal, Manish Gautam, Tijesunimi Abiola, Hassan Burhan
Journal: European Respiratory Journal (2011)

Introduction:  Various biochemical and radiological tests have been studied in recent years for an accurate and early diagnosis of pulmonary embolism (PE). As well as D-dimers, Troponin level has been noted to be raised in confirmed PE.   Aim:  To study routine biochemical test results as predictors of PE.   Method:  Routine biochemical results of all patients investigated with a computed tomography pulmonary angiogram (CTPA) for suspected PE at our 960 bed university hospital from February 2008 to January 2009 were analysed.   Results:  Of the total of 666 CTPAs performed, reports and routine blood results for 576 patients were collected and analysed:   Discussion:  Our results may have been influenced by some patients having other significant pathologies and by the fact that not all patients had all the blood tests done.  An elevated D-dimer was not found to be significantly associated with a diagnosis of PE in our study. Troponin and CRP also had no diagnostic significance. Raised Urea, integral to the severity scoring in community acquired pneumonia, was, however, significant.
Actin Capping Protein
Authors: W. Glen Pyle, Marilyn C. Hart, John A. Cooper, Marius P. Sumandea, Pieter P. de Tombe, R. John Solaro
Journal: Circulation Research (2002)

Actin capping protein (CapZ) binds the barbed ends of actin at sarcomeric Z-lines. In addition to anchoring actin, Z-discs bind protein kinase C (PKC). Although CapZ is crucial for myofibrillogenesis, its role in muscle function and intracellular signaling is unknown. We hypothesized that CapZ downregulation would impair myocardial function and disrupt PKC-myofilament signaling by impairing PKC–Z-disc interaction. To test these hypotheses, we examined transgenic (TG) mice in which cardiac CapZ protein is reduced. Fiber bundles were dissected from papillary muscles and detergent extracted. Some fiber bundles were treated with PKC activators phenylephrine (PHE) or endothelin (ET) before detergent extraction. We simultaneously measured Ca 2+ -dependent tension and actomyosin MgATPase activity. CapZ downregulation increased myofilament Ca 2+ sensitivity without affecting maximum tension or actomyosin MgATPase activity. Maximum tension and actomyosin MgATPase activity were decreased after PHE or ET treatment of wild-type (WT) muscle. Fiber bundles from TG hearts did not respond to PHE or ET. Immunoblot analysis revealed an increase in myofilament-associated PKC-ε after PHE or ET exposure of WT preparations. In contrast, myofilament-associated PKC-ε was decreased after PHE or ET treatment in TG myocardium. Protein levels of myofilament-associated PKC-β were decreased in TG ventricle. C-protein and troponin I phosphorylation was increased after PHE or ET treatment in WT and TG hearts. Basal phosphorylation levels of C-protein and troponin I were higher in TG myocardium. These results indicate that downregulation of CapZ, or other changes associated with CapZ downregulation, increases cardiac myofilament Ca 2+ sensitivity, inhibits PKC-mediated control of myofilament activation, and decreases myofilament-associated PKC-β.
The Biology of NKT Cells
Authors: Albert Bendelac, Paul B. Savage, Luc Teyton
Journal: Annual Review of Immunology (2006)

Recognized more than a decade ago, NKT cells differentiate from mainstream thymic precursors through instructive signals emanating during TCR engagement by CD1d-expressing cortical thymocytes. Their semi-invariant alphabeta TCRs recognize isoglobotrihexosylceramide, a mammalian glycosphingolipid, as well as microbial alpha-glycuronylceramides found in the cell wall of Gram-negative, lipopolysaccharide-negative bacteria. This dual recognition of self and microbial ligands underlies innate-like antimicrobial functions mediated by CD40L induction and massive Th1 and Th2 cytokine and chemokine release. Through reciprocal activation of NKT cells and dendritic cells, synthetic NKT ligands constitute promising new vaccine adjuvants. NKT cells also regulate a range of immunopathological conditions, but the mechanisms and the ligands involved remain unknown. NKT cell biology has emerged as a new field of research at the frontier between innate and adaptive immunity, providing a powerful model to study fundamental aspects of the cell and structural biology of glycolipid trafficking, processing, and recognition.
Social and Nonsocial Cognition in Bipolar Disorder and Schizophrenia: Relative Levels of Impairment
Authors: Junghee Lee, Lori Altshuler, David C. Glahn, David J. Miklowitz, Kevin Ochsner, Michael F. Green
Journal: American Journal of Psychiatry (2013)

Objective This study aimed to determine the relative extent of impairment in social and nonsocial cognitive domains in patients with bipolar disorder compared with schizophrenia patients and healthy comparison subjects. Methods Sixty-eight clinically stable outpatients with bipolar disorder, 38 clinically stable outpatients with schizophrenia, and 36 healthy comparison subjects completed a range of social (facial affect perception, emotional regulation, empathic accuracy, mental state attribution, and self-referential memory) and nonsocial (speed of processing, attention/vigilance, working memory, verbal memory, visual memory, and reasoning/problem solving) cognitive tasks. Results For each social cognitive task, patients with bipolar disorder did not differ significantly from comparison subjects, and both groups performed better than schizophrenia patients. Within the bipolar group, clinical features and medication status were not related to social cognitive performance. Bipolar patients showed performance patterns across tasks (i.e., profiles) that were similar to those of comparison subjects on both social and nonsocial cognitive domains, whereas both groups differed from schizophrenia patients for both domains. Regarding relative impairment across the two cognitive domains, results revealed a significant group-by-domain interaction in which bipolar patients showed less impaired social than nonsocial cognition, while schizophrenia patients showed the opposite pattern. Conclusions Bipolar patients showed less impairment on social relative to nonsocial cognitive performance, whereas schizophrenia patients showed more impairment on social relative to nonsocial cognitive performance. These results suggest that these two cognitive domains play different roles in bipolar disorder compared with in schizophrenia.
Expression of vascular endothelial growth factor in patients with acute myocardial infarction
Authors: Yukihiro Hojo, Uichi Ikeda, Yun Zhu, Motoi Okada, Shuichi Ueno, Hiroshi Arakawa, Hideyuki Fujikawa, Taka-aki Katsuki, Kazuyuki Shimada
Journal: Journal of the American College of Cardiology (2000)
Central and peripheral vasopressin interact differently with sympathetic nervous system and renin-angiotensin system in renal hypertensive rabbits.
Authors: H Kumagai, H Suzuki, M Ichikawa, Y Matsumura, M Jimbo, M Ryuzaki, T Saruta
Journal: Circulation Research (1993)

This study was designed to elucidate how central and peripheral arginine vasopressin (AVP) interacts with the sympathetic nervous system and the renin-angiotensin system to maintain blood pressure in two-kidney, one-clip hypertensive rabbits. We recorded renal sympathetic nerve activity (RSNA) in the conscious state as an index of sympathetic nervous system function. The changes in mean arterial pressure, heart rate, and RSNA were recorded continuously for 60 minutes after intravenous administrations of captopril (2.5 mg/kg) and nicardipine (3.2 micrograms.kg-1.min-1) in eight identical rabbits. Despite equivalent reductions in mean arterial pressure (10 +/- 1 mm Hg), the increase in RSNA was significantly larger with captopril than that with nicardipine, and the plasma concentration of AVP was elevated (from 100% to 255 +/- 24%) with captopril. Mean arterial pressure was reduced, and RSNA was increased by intravenous infusion of AVP antagonist d(CH2)5Tyr(Me)AVP (n = 8), whereas vertebral artery infusion of the antagonist (n = 6) did not change RSNA. During central and peripheral infusions of AVP antagonist, RSNA was exaggerated by blood pressure reduction with nicardipine as well as with captopril. Increases in RSNA induced by captopril and nicardipine were larger by central infusion of AVP antagonist than by intravenous infusion. The decrease in mean arterial pressure by captopril (30 +/- 4 mm Hg) in eight sinoaortic-denervated hypertensive rabbits was larger than that in hypertensive rabbits with intact baroreflex. These data suggest that compensatory activation of RSNA was revealed by central and peripheral attenuation of AVP and that the sympathetic nervous system became the most important mechanism for blood pressure maintenance in the absence of AVP. The interaction of AVP with the sympathetic nervous system may be independent of the state of the renin-angiotensin system, since the exaggeration of RSNA by AVP antagonist was qualitatively the same with nicardipine as with captopril. In conscious renal-hypertensive rabbits, AVP in the central nervous system played a substantial role when blood pressure was reduced, although it did not contribute to blood pressure maintenance in the basal condition.
Prevention of in vitro neutrophil-endothelial attachment through shedding of L-selectin by nonsteroidal antiinflammatory drugs.
Authors: F Díaz-González, I González-Alvaro, M R Campanero, F Mollinedo, M A del Pozo, C Muñoz, J P Pivel, F Sánchez-Madrid
Journal: Journal of Clinical Investigation (1995)

The activation of the endothelial cells by extravascular stimuli is the key event in the extravasation of circulating leukocytes to target tissues. L-selectin, a member of the selectin family, is constitutively expressed by white cells, and is the molecule involved in the initial binding of leukocytes to activated endothelium. After activation, leukocytes rapidly release L-selectin from the cell surface, suggesting that the functional activity of this molecule is controlled in large part by its appearance and disappearance from cell surface. We have studied in a neutrophil-activated endothelial cell binding assay, the effect of different antiinflammatory drugs (steroidal and nonsteroidal) in the L-selectin-mediated interaction of neutrophils with activated endothelial cells. Some nonsteroidal antiinflammatory drugs (NSAIDs), such as indomethacin, diclofenac, ketoprofen, and aspirin, but not steroids, strongly inhibited the neutrophil-endothelial cell attachment. Furthermore, we also investigated the underlying mechanism of this functional effect. The expression of L-selectin on the neutrophil surface rapidly decreased in the presence of different NSAIDs, in a dose- and time-dependent manner, whereas no changes in the expression of other adhesion molecules such as CD11a, CD11b, CD31, or ICAM-3 (CD50) were observed. Interestingly, studies in vivo on healthy volunteers treated with physiological doses of indomethacin showed a significant decrease of L-selectin neutrophil expression. Only diclofenac induced an upregulation of CD11b expression, suggesting an activating effect on neutrophils. No enzyme release was observed upon treatment of neutrophils with different NSAIDs, indicating a lack of degranulatory activity of NSAIDs, with the exception of diclofenac. The downregulation of L-selectin expression was due to the rapid cleavage and shedding of the membrane L-selectin, as determined by both immunoprecipitation from 125I-labeled neutrophils, and quantitative estimation in cell-free supernatants. These results suggest that NSAIDs exert a specific action on adhesion receptor expression in neutrophils, which might account, at least in part, for the antiinflammatory activities of NSAIDs.
Further characterization of the thrombasthenia-related idiotype OG. Antiidiotype defines a novel epitope(s) shared by fibrinogen B beta chain, vitronectin, and von Willebrand factor and required for binding to beta 3.
Authors: Y Gruel, E Brojer, D J Nugent, T J Kunicki
Journal: The Journal of Experimental Medicine (1994)

A patient (OG) with Glanzmann thrombasthenia became refractory to platelet transfusion after the production of an immunoglobulin G (IgG) isoantibody (Ab1) specific for the integrin subunit beta 3. To determine the frequency at which the OG idiotype is found in the general population and in immune-mediated disease states, we developed a rabbit polyclonal antibody (Ab2) specific for affinity-purified OG anti-beta 3 Fab. The binding of Ab2 to Ab1 is inhibited by purified alpha IIb beta 3. Ab2 als binds to IgG specific for alpha IIb beta 3 obtained from one nonrelated Glanzmann thrombasthenia patient ES who has developed isoantibodies of similar specificity. On the other hand, Ab2 does not recognize alpha IIb beta 3-specific antibodies produced by two Glanzmann thrombasthenia patients, AF and LUC, who have developed isoantibodies with specificities distinct from that of the OG isoantibody. Moreover, Ab2 does not recognize alpha IIb beta 3-specific antibodies developed by three representative patients with (autoimmune) thrombocytopenic purpura or six representative patients with alloimmune thrombocytopenias, nor does it bind to IgG from any of 13 nonimmunized individuals. We have found that Ab2 also binds to selected protein ligands of alpha IIb beta 3 namely, fibrinogen, vitronectin, and von Willebrand factor, but not to other protein ligands or control proteins, such a fibronectin, type I collagen, and albumin. The epitope(s) recognized by Ab2 on each adhesive protein are either very similar or identical since each protein can inhibit the binding of Ab2 to any of the other proteins. The epitope on fibrinogen recognized by Ab2 resides in the B beta chain, and is likely contained within the first 42 amino acids from the NH2 terminus. Since OG IgG inhibits fibrinogen binding to alpha IIb beta 3, the specificity of the OG idiotype defines a novel binding motif for the integrin alpha IIb beta 3 that is shared by fibrinogen, vitronectin, and von Willebrand factor, but distinct from previously described RGD-containing sites on the fibrinogen, A alpha chain or the fibrinogen gamma chain COOH-terminal decapeptide site. Our findings reported here represent an excellent example of molecular mimicry in which an antigen-selected, IgG inhibitor of alpha IIb beta 3 function shares a novel recognition sequence common to three physiologic protein ligands of that receptor.
Seasonal Variation in Month of Birth and Diagnosis of Early Childhood Acute Lymphoblastic Leukemia
Authors: Henrik Toft Sørensen
Journal: JAMA (2001)

To the Editor: I concur with Dr Petty1 regarding lung cancer screening. Epidemiology is important, but it can sometimes obscure variations in individual disease. Survival is not only related to tumor size but also to tumor biology and behavior and individual immune responses.
Coronary Artery Involvement in Children With Kawasaki Disease
Authors: Brian W. McCrindle, Jennifer S. Li, L. LuAnn Minich, Steven D. Colan, Andrew M. Atz, Masato Takahashi, Victoria L. Vetter, Welton M. Gersony, Paul D. Mitchell, Jane W. Newburger
Journal: Circulation (2007)

Most studies of coronary artery involvement and associated risk factors in Kawasaki disease have used the Japanese Ministry of Health dichotomous criteria. Analysis of serial normalized artery measurements may reveal a broader continuous spectrum of involvement and different risk factors.Clinical, laboratory, and echocardiographic measurements obtained at baseline and 1 week and 5 weeks after presentation were examined in 190 Kawasaki disease patients as part of a clinical trial of primary therapy with pulse steroids in addition to standard intravenous immunoglobulin. Maximum coronary artery z score normalized to body surface area was significantly greater than normal at all time points, decreasing significantly over time from baseline. A maximal z score > or = 2.5 at any time was noted in 26% of patients. Japanese Ministry of Health dimensional criteria were met by 23% of patients. Significant independent factors associated with greater z score at any time included younger patient age, longer interval from disease onset to treatment with intravenous immunoglobulin, lower serum IgM level at baseline, and lower minimum serum albumin level. z scores of the proximal right coronary artery were higher than those in the left anterior descending branch.Analyses of serial normalized coronary artery measurements in optimally treated Kawasaki disease patients demonstrated that for most patients, measurements are greatest at baseline and subsequently diminish; baseline measurements appear to be good predictors of involvement during early follow-up. When a more precise assessment is used, risk factors for coronary artery involvement are similar to those defined with arbitrary dichotomous criteria.
Interferon-α and zidovudine combination therapy for chronic hepatitis B: Results of a randomized, placebo-controlled trial
Authors: Harry L. A. Janssen, Luuk Berk, Rudolf A. Heijtink, Fiebo J. W. Ten Kate, Solko W. Schalm
Journal: Hepatology (1993)

Interferon-alpha therapy leads to HBeAg seroconversion in only one third of patients with chronic hepatitis B. In an attempt to increase the seroconversion rate, we investigated the combination of interferon-alpha and zidovudine in a subset of patients with presumably low response rates for interferon-alpha monotherapy. In a double-blind, controlled trial, 24 HBeAg-positive patients were randomized to receive lymphoblastoid interferon-alpha in subcutaneous doses increasing to 5 MU daily, combined with zidovudine given orally in doses increasing from 500 to 1,000 mg/day or with placebo for 16 wk. Treatment effects were monitored by quantitative assessment of HBV DNA, HBeAg and HBV DNA polymerase. Six months after termination of therapy, 1 of 12 (8%; 95% confidence interval = 2% to 39%) patients treated with interferon-alpha plus zidovudine and 2 of 12 (17%; 95% confidence interval 2% to 48%) patients from the control group exhibited responses (HBeAg seroconversion). All patients remained HBsAg positive. The only responder of the interferon-alpha-zidovudine group relapsed after cessation of therapy, so none of the zidovudine-treated patients were HBeAg negative at the end of follow-up. No significant difference in AST level or in any of the virological markers was observed between the two groups during the course of the study. Adverse effects (anemia, leukopenia) necessitated reduction in the dose of zidovudine in 50% and of interferon-alpha in 42% of the patients treated with interferon-alpha plus zidovudine; in the control group these rates were 0% for placebo and 8% for interferon-alpha. In conclusion, the antiviral effect of interferon-alpha in chronic hepatitis B was not enhanced by additional zidovudine treatment. The combination therapy induced considerable side effects leading to dose reduction for both zidovudine and interferon-alpha. For combination therapy with interferon-alpha, oral nucleoside analogs with more potent antiviral effects and less toxicity than zidovudine should be developed.