bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of Rho Kinase Isoforms in Lung Endothelial Cells during Inflammation
Authors: Mong Phyllus Y. , Wang Qin 
Published: February 2009

Abstract
Rho kinase (ROCK) is a downstream effector of Rho family GTPases, and two highly homologous isoforms, ROCK1 and ROCK2, are similarly inhibited by the widely used pharmacologic inhibitors. In endothelial cells (ECs), activation of ROCK regulates myosin L chain (MLC) phosphorylation, stress fiber formation and permeability increases during inflammation. This study examined isoform-specific ROCK activation in lung ECs in vitro using human pulmonary microvascular ECs and ex vivo using freshly isolated lung ECs from mice. In unstimulated human as well as mouse lung ECs, ROCK2 activity was greater than ROCK1 activity. TNF-α stimulation induced activation of both ROCK1 and ROCK2 in cultured human ECs. Studies using lung ECs freshly isolated from mice showed that intratracheal instillation of LPS induced ROCK activation in lung ECs that was inhibited by treating animals with fasudil, a pharmacologic ROCK inhibitor, and that both ROCK1 and ROCK2 were activated. Small interference RNA targeting ROCK1 or ROCK2 was used to examine their functions in regulating MLC phosphorylation and permeability increases induced by TNF-α in human ECs. TNF-α-induced MLC phosphorylation required ROCK activation. Inhibition of ROCK1 alone was not sufficient to prevent TNF-α-induced MLC phosphorylation, whereas inhibition of ROCK2 prevented TNF-α-induced late MLC phosphorylation at 24 h. Although ROCK1 was dispensable for TNF-α-induced MLC phosphorylation, ROCK1 was required for TNF-α-induced early permeability increases. Therefore, ROCK1 and ROCK2 are both activated by TNF-α and can be functionally separated in the signaling pathways leading to TNF-α-induced MLC phosphorylation and permeability increases.
Myosin-IIA and ICAM-1 Regulate the Interchange between Two Distinct Modes of T Cell Migration
Authors: Jacobelli Jordan , Bennett F. Chris , Pandurangi Priya , Tooley Aaron J. , Krummel Matthew F. 
Published: February 2009

Abstract
How T cells achieve rapid chemotactic motility under certain circumstances and efficient cell surface surveillance in others is not fully understood. We show that T lymphocytes are motile in two distinct modes: a fast “amoeboid-like” mode, which uses sequential discontinuous contacts to the substrate; and a slower mode using a single continuously translating adhesion, similar to mesenchymal motility. Myosin-IIA is necessary for fast amoeboid motility, and our data suggests that this occurs via cyclical rear-mediated compressions that eliminate existing adhesions while licensing subsequent ones at the front of the cell. Regulation of Myosin-IIA function in T cells is thus a key mechanism to regulate surface contact area and crawling velocity within different environments. This can provide T lymphocytes with motile and adhesive properties that are uniquely suited toward alternative requirements for immune surveillance and response.
Activation of Mammalian Target of Rapamycin Controls the Loss of TCRζ in Lupus T Cells through HRES-1/Rab4-Regulated Lysosomal Degradation
Authors: Fernandez David R. , Telarico Tiffany , Bonilla Eduardo , Li Qing , Banerjee Sanjay , Middleton Frank A. , Phillips Paul E. , Crow Mary K. , Oess Stefanie , Muller-Esterl Werner , Perl Andras 
Published: February 2009

Abstract
Persistent mitochondrial hyperpolarization (MHP) and enhanced calcium fluxing underlie aberrant T cell activation and death pathway selection in systemic lupus erythematosus. Treatment with rapamycin, which effectively controls disease activity, normalizes CD3/CD28-induced calcium fluxing but fails to influence MHP, suggesting that altered calcium fluxing is downstream or independent of mitochondrial dysfunction. In this article, we show that activity of the mammalian target of rapamycin (mTOR), which is a sensor of the mitochondrial transmembrane potential, is increased in lupus T cells. Activation of mTOR was inducible by NO, a key trigger of MHP, which in turn enhanced the expression of HRES-1/Rab4, a small GTPase that regulates recycling of surface receptors through early endosomes. Expression of HRES-1/Rab4 was increased in CD4+ lupus T cells, and in accordance with its dominant impact on the endocytic recycling of CD4, it was inversely correlated with diminished CD4 expression. HRES-1/Rab4 overexpression was also inversely correlated with diminished TCRζ protein levels. Pull-down studies revealed a direct interaction of HRES-1/Rab4 with CD4 and TCRζ. Importantly, the deficiency of the TCRζ chain and of Lck and the compensatory up-regulation of FcεRIγ and Syk, which mediate enhanced calcium fluxing in lupus T cells, were reversed in patients treated with rapamcyin in vivo. Knockdown of HRES-1/Rab4 by small interfering RNA and inhibitors of lysosomal function augmented TCRζ protein levels in vitro. The results suggest that activation of mTOR causes the loss of TCRζ in lupus T cells through HRES-1/Rab4-dependent lysosomal degradation.
Blocking Development of a CD8+ T Cell Response by Targeting Lymphatic Recruitment of APC
Authors: Teoh Denise , Johnson Louise A. , Hanke Tomas , McMichael Andrew J. , Jackson David G. 
Published: February 2009

Abstract
Generating a protective immune response to viral infection is known to depend upon the priming and clonal expansion of virus-specific CD8+ T cells by Ag-loaded dendritic cells (DC) within secondary lymphoid tissue. However, the actual initiation of the response involves critical upstream events that control the recruitment of mature Ag-charged DC from the periphery via afferent lymphatics, events that are still only partly understood. Recent evidence has revealed that transmigration of lymphatic endothelium by DC is regulated by the adhesion molecules ICAM-1 and VCAM-1 both in vitro and in vivo. These findings imply that lymphatic entry may be an important rate-limiting step in primary immunity and a possible target for immune intervention. In this study, we have explored such possibilities using an F5 TCR-transgenic mouse model to assess the contribution of lymphatic cell adhesion molecules in the CD8+ T cell response to influenza virus nucleoprotein (NP). We show for the first time that immunization with ICAM-1- and VCAM-1-blocking mAbs can impair the T cell response in lymph node-draining sites of dermally administered nucleoprotein vaccine (MVA.HIVA.NP) by targeting lymphatic uptake of Ag-loaded DC ahead of other cell adhesion molecule-dependent events. These results reveal lymphatic entry as an important step that may be rate limiting in the development of immunity and reconfirm its potential as a target for localized immunotherapy in inflammation and tissue rejection.
A Role of IgM Antibodies in Monosodium Urate Crystal Formation and Associated Adjuvanticity
Authors: Kanevets Uliana , Sharma Karan , Dresser Karen , Shi Yan 
Published: February 2009

Abstract
Uric acid is released from injured cells and can act as an adjuvant signal to the immune system. Uric acid crystals invoke strong inflammatory responses in tissues. Although their biological effects are evident and the associated signaling mechanisms are becoming clear, it remains unexplained as to why uric acid precipitates rapidly in vivo, in sharp contrast to the minimal crystallization in vitro. We report in this study that a group of IgM Abs is able to bind to these crystals, which is interesting in light that B cell-deficient mice do not sense the proinflammatory adjuvant effect of uric acid. The titers of these Abs increase upon immunization with uric acid crystals. We have produced large quantities of such mAbs. The purified IgM Abs can significantly facilitate uric acid precipitation to form the inflammatory crystals in vitro. Infusion of these Abs into B cell-deficient mice significantly increases the basal level of inflammation in these recipients and restores the host’s ability to sense uric acid’s adjuvanticity. Therefore, we have identified a factor in determining uric acid precipitation and possibly its ability to function as an endogenous adjuvant. This finding suggests a new mechanism of the pathogenesis of gouty arthritis and uric acid-induced immune activation.
Detection of Rh antibodies using two low ionic diluents
Authors: Skaik YA 
Published: February 2009

Background:
Low ionic strength solution (LISS) is used to increase the rate of association of antibody to the corresponding antigen during antibody detection tests. A number of LISSs are available on the market.

Aims:
The efficiency of two commercial low ionic diluents, DiaMed ID-CellStab and Inverclyde LISS were assessed using the DiaMed-ID LISS Coombs microtube column system and an incubation time varying from 15 to 35 min.

Materials and Methods:
One-hundred samples containing five Rh antibodies (anti-D, anti-C, anti-E, anti-c and anti-e) were tested against commercial red cells using the two low ionic diluents after 15, 25 and 35 min.

Results:
The Inverclyde LISS detected 91, 95 and 96% of the Rh antibodies compared to 78, 79 and 83% for ID-CellStab after 15, 25 and 35 min incubation time, respectively, for both methods.

Conclusions:
The Inverclyde LISS is a more suitable and efficient diluent than ID-CellStab for the detection of Rh antibodies. The sensitivity of Rh antibody detection increased for the both methods as the incubation time increased.
Immunophenotypic characterisation of peripheral T lymphocytes in pulmonary tuberculosis
Authors: Al Majid FM , Abba AA 
Published: February 2009

Background:
The cellular immune response plays an important role in determining the outcome of infection and disease in Mycobacterium tuberculosis. Many studies of these disease interactions yield contradictory results.

Aim:
This study aims at determining the changes that take place in the subpopulations of T lymphocytes in the blood of patients with pulmonary tuberculosis (TB).

Settings and Design:
This cross-sectional study was done at King Khalid University Hospital, Riyadh, Saudi Arabia.

Materials and Methods:
Flow cytometry was used to determine the absolute numbers and percentages of T CD3, T CD4, T CD8, T CD19 and natural killer (NK) T cells in 54 patients with active pulmonary TB before the commencement of treatment and in 25 healthy PPD negative volunteers.

Statistical Analysis:
Statistical Package for Social Sciences (version 11.5) was used for analysis.

Results:
There were significant differences in the values of CD3, CD4 and NK T cells among the groups. The numbers of CD3 and CD4 cells were lower in subjects than in controls [1091.9 ± 321.4 vs. 1364.6 ± 251.2; P < 0.001 and 639.8 ± 285 vs. 822 ± 189.9; P < 0.004, respectively] while numbers of NK T cells were much higher in patients than in controls (410.7 ± 286 vs. 182.3 ± 140; P < 0.001). The numbers of CD8 cells were not significantly changed with disease (609 ± 233.5 in subjects and 613.4 ± 170.3 in controls P = 0.761).

Conclusion:
There are significant changes in the cellular immune response particularly affecting the CD3, CD4 and NK T cells with the development of pulmonary TB. Therefore, further studies of these changes may have important implications on the development of diagnostic tools, vaccines and treatment modalities.
Relative efficiency of polymerase chain reaction and enzyme-linked immunosorbant assay in determination of viral etiology in congenital cataract in infants
Authors: Shyamala G , Sowmya P , Madhavan HN , Malathi J 
Published: February 2009

Background:
Perinatal viral infections of fetus are among the leading causes of congenital cataract and identifying the viral etiology is important. Objectives: To detect the presence of Rubella virus (RV), herpes simplex virus (HSV) and cytomegalovirus (CMV) in lens aspirate specimens obtained from patients with congenital cataract and relate the results with serology.

Setting and Design:
Prospective study carried out in tertiary care hospital.

Materials and Methods:
Fifty lens aspirates from 50 infants with congenital cataract were subjected to HSV, RV isolation and polymerase chain reaction (PCR) for detection of HSV and CMV. Reverse transcription polymerase chain reaction (RT-PCR) was applied for RV detection. Peripheral blood specimens were screened for anti-HSV, RV and CMV antibodies by enzyme-linked immunosorbant assay (ELISA).

Results:
Rubella virus was detected in nine (18%) lens aspirates, by nRT-PCR which includes six positive by culture. HSV-2 DNA was detected in nine other lens aspirates, while CMV was not detected by PCR. Serological results did not correlate with the presence of viruses in the lens aspirates. This is the first report of detection of HSV-2 DNA in cases of congenital cataract.

Conclusions:
Cytomegalovirus may not be playing a significant role in causation of congenital cataract. The role of serology in identifying causative viral infection for congenital cataract needs to be re-evaluated.
Stomaplasty-anterior advancement flap and lateral splaying of trachea, a simple and effective technique
Authors: Trivedi NP , Patel D , Thankappan K , Iyer S , Kuriakose MA 
Published: February 2009

Background:
Stomal stenosis after laryngectomy is a common and distressing complication. Once sets in, it is generally progressive, causes problems and needs active intervention.

Aim:
To evaluate effectiveness of new simple method of stomaplasty in solving troublesome complication of stoma stenosis.

Settings and Design:
Charts of eight patients who underwent modified stomaplasty and completed 1 year were reviewed.

Materials and Methods:
A modified anterior advancement flap and lateral splaying of trachea for stoma plasty are described. This involves excision of scar tissue of the anterior two-third of trachea and interposition of the defect with an inferiorly based triangular skin flap. The tracheo-esophageal-prosthesis (TEP) site is left untouched.

Statistical Analysis:
Outcome were measured in relation with need for further stenting or any other revision procedure required and ability to use TEP for speech production.

Results:
Eight patients underwent stoma revision surgery. Median preprocedure stoma diameter was 10 mm vertically (range 8-12 mm) and 6 mm horizontally (range 5-10 mm). This could be improved to 25 mm (range 22-30 mm) vertically and 16 mm (range 14-20 mm) horizontally after stoma revision. At 1-year follow-up, the median measurements were 20 mm (range 16-26) vertically and 14 mm (range 12-18) horizontally. Postprocedure, one patient required intermittent stenting at nighttime. All patients could use the TEP effectively. One patient who underwent salvage laryngectomy following chemoradiotherapy developed flap dehiscence.

Conclusions:
This is a simple and effective technique for stomaplasty. All patients treated with this technique had adequately large stoma for breathing and use of TEP.
Patient-controlled epidural analgesia with fentanyl and bupivacaine provides better analgesia than intravenous morphine patient-controlled analgesia for early thoracotomy pain
Authors: Behera BK , Puri GD , Ghai B 
Published: February 2009

Background:
Intravenous patient-controlled analgesia (IVPCA) and patient-controlled epidural analgesia (PCEA) were studied in terms of analgesic efficacy, respiratory function and side effects after thoracic surgery for 24h. PCEA using fentanyl and bupivacaine as compared to IVPCA using morphine provides better pain relief both at rest and during coughing and is associated with fewer side effects.

Aims:
To compare IVPCA and PCEA in terms of analgesic efficacy, respiratory function and side effects after thoracic surgery.

Settings and Design:
Tertiary care teaching hospital. Prospective, randomized and open study.

Materials and Methods:
Thirty ASA-I or II patients undergoing thoracotomy were assigned randomly to receive either IVPCA using morphine or PCEA using fentanyl and bupivacaine combination postoperatively. No background infusion was administered in either group. Postoperative evaluation included pain intensity both at rest and during coughing, degree of sedation, arterial blood gas, forced vital capacity (FVC), peak expiratory flow rate (PEFR), presence of side effects such as nausea/vomiting and pruritis at 0, 2, 8, 12 and 24h. The primary outcome of the study was the percentage of patients with analgesia failure defined as VAS>30 despite three consecutive PCA boluses requiring rescue analgesia with intravenous fentanyl.

Statistical Analysis:
Data were analyzed using t -test, χ2 test and Mann-Whitney test.

Results:
Significantly less number of patients required rescue analgesia in PCEA group (P<0.05). Pain relief was better both at rest and during coughing (P<0.05) in PCEA group as compared to IVPCA. Patients in the PCEA group were less sedated and had fewer incidences of side effects, i.e. nausea/vomiting and pruritis. Postoperative FVC and PEFR were reduced significantly compared to baseline only in IVPCA group (P<0.05). Conclusion: After thoracic surgery, PCEA using fentanyl and bupivacaine as compared to IVPCA using morphine provides better pain relief both at rest and during coughing and associated with fewer side effects.
Family burden, quality of life and disability in obsessive compulsive disorder
Authors: Gururaj GP , Math SB , Reddy JYC , Chandrashekar CR 
Published: February 2009

Background:
Obsessive compulsive disorder (OCD) is a psychiatric disorder that often tends to run a chronic course. The lifetime prevalence of OCD is around 1-3%, which is twice as prevalent as schizophrenia and bipolar disorder.

Aim:
To asses the family burden, quality of life (QoL) and disability in patients suffering from at least moderately ill OCD and then to compare them with schizophrenia patients of comparable severity.

Settings and Design:
We recruited 70 consecutive subjects (OCD=35, schizophrenia=35) who met study criteria between March 2005 and March 2006 from the psychiatric services of the National Institute of Mental Health and Neuro Sciences, Bangalore, India.

Materials and Methods:
The severity of illness was rated using the Clinical Global Impression-Severity (CGI-S). Instruments used in the current study were the Family Burden Schedule, the World Health Organization (WHO) QoL (Bref) and the WHO - Disability Assessment Schedule (DAS).

Statistical Analysis:
The Fisher's exact test/chi-square test was used to compare categorical variables and the independent sample t test was used to analyze continuous variables. Analysis of covariance (ANCOVA) was used to compare the groups after controlling for potential confounding variables. Pearson's correlation was used for correlation analysis.

Results:
Overall family burden, financial burden and disruption of family routines were significantly higher in schizophrenia patients compared to OCD although the groups did not differ with respect to other domains of family burden. On the WHO QoL, OCD patients were comparable to schizophrenia patients with respect to the psychological and social domains. On the WHO - DAS, both the groups were similar in all the domains except getting around.

Conclusion:
Severe OCD is associated with significant disability, poor QoL and high family burden, often comparable to schizophrenia. Therefore, there is an urgent need to increase the sensitivity among healthcare professionals to recognize and treat OCD.
Pulmonary function profile in patients with benign goiters without symptoms of respiratory compromise and the early effect of thyroidectomy
Authors: Pradeep PV , Tiwari P , Mishra A , Agarwal G , Agarwal A , Verma AK , Mishra SK 
Published: February 2009

Background:
A large number of patients in our country develop goiters which seem to be apparently asymptomatic. Conventional radiography does not address the abnormal air flow dynamics. Flow volume loop studies have shown characteristic dampening of both inspiratory and expiratory curves. Pulmonary function tests (PFT) can provide a simple noninvasive method of assessing airway compromise.

Aim:
To address the effect of longstanding asymptomatic, benign goiter by performing PFT on the preoperative airway dynamics and the early postoperative changes at six weeks.

Setting and Design:
Tertiary care center, Prospective study. Materials and Methods: Sixty-four patients with benign goiters were included after they satisfied the necessary exclusion and inclusion criteria. Pulmonary function tests were performed in the pre and postoperative period.

Statistical Analysis Used:
SPSS ver. 10 software, Pearson's Bivariate correlation and students T test. Results: The preoperative PFT showed significant reduction in the Vital capacity (VC), Forced Vital Capacity (FVC), Forced expiratory volume in one second (FEV1), mid expiratory flow (MEF 25) and MEF 50 in the females and VC, FVC and FEV1 in males. Postoperatively significant improvement was observed in the tidal volume (VT) and FEV1 in the females and airway resistance in males.

Conclusions:
Pulmonary function tests can demonstrate the unmanifested abnormal airflow dynamics in benign asymptomatic goiters, which would have otherwise taken years to manifest. This abnormality improved after thyroidectomy, especially the forced expiratory maneuvers. The duration and weight of the goiter correlated well with reduction in FEV1 and its subsequent improvement after surgery in females.
Fournier′s gangrene
Authors: Unalp HR , Kamer E , Derici H , Atahan K , Balci U , Demirdoven C , Nazli O , Onal MA 
Published: February 2009

Context:
Fournier's gangrene (FG) is a rapidly progressing acute gangrenous infection of the anorectal and urogenital area.

Aims:
The objectives of this study were to investigate patients with FG and to determine risk factors that affect mortality.

Settings and Design:
Retrospective clinical study.

Materials and Methods:
Clinical presentations and outcomes of surgical treatments were evaluated in 68 patients with FG.

Statistical Analysis Used:
Chi-square, Student's t -test, and logistic regression test.

Results:
Mean age of patients was 54 and female-to-male ratio was 9:59. Among the predisposing factors, diabetes mellitus (DM) was the most common (n =24, 35.3%), and sepsis on admission was detected in 31 (45.6%) and 15 (22.1%) patients, respectively. Seven (10.3%) patients died. Using logistic regression test, Fournier's Gangrene Severity Index (FGSI) <9, DM and sepsis on admission were found as prognostic factors. Conclusions: FG has a high mortality rate, especially in patients with DM and sepsis. An FGSI value <9 indicates high mortality rate.