bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of selected neuropeptides in pathogenesis of atopic dermatitis
Authors: Salomon J , Baran E
Published: September 2007

Background  Atopic dermatitis (AD) is an inflammatory skin disease of a chronic course. The role of neuropeptides in pathogenesis of this disorder is probably not crucial; however, there is evidence that these substances influence the development and course of AD.

Objective  The aim of this study was to evaluate the plasma level of substance P, neuropeptide Y (NPY) and calcitonin gene related peptide (CGRP) in AD patients during exacerbation and remission of the disease.

Material and methods  Forty‐nine patients with AD, aged 17 to 56 years, participated in the study. Among this group, there were 25 males (51%) and 24 females (49%). The disease lasted from 1 to 55 years. The severity of the disease was assessed with SCORAD index. The severity of pruritus was evaluated with Visual Analog Scale and a specially designed questionnaire. Neuropeptides plasma level was detected with radioimmunoassay.

Results  Substance P plasma level in AD patients during exacerbation and remission was significantly higher than in the control group. There was a negative correlation between substance P plasma level and total IgE level. CGRP plasma level during exacerbation of AD was significantly lower than in healthy controls and increased in the remission. Significantly higher CGRP concentration was observed in patients suffering from severe pruritus; however, both in patients with more and less severe pruritus, CGRP plasma level was lower than in controls. Higher CGRP plasma level was also observed in patients with more severe disease. NPY plasma level in patients with AD was significantly increased both during exacerbation and remission. During remission of AD, NPY concentration was higher than during exacerbation.
Haptoglobin from psoriatic patients exhibits decreased activity in binding haemoglobin and inhibiting lecithin‐cholesterol acyltransferase activity
Authors: Cigliano L , Maresca B , Salvatore A , Nino M , Monfrecola G , Ayala F , Carlucci A , Pugliese RC , Pedone C , Abrescia P
Published: September 2007

Objective  The aim of this work was to assess whether psoriasis is associated with phenotype prevalence and altered activity of haptoglobin (Hpt).

Background  Hpt is a plasma acute‐phase glycoprotein, displaying in humans three phenotypes. Phenotype prevalence or structure modification of Hpt was associated with several diseases. The Hpt main function is to bind and carry to the liver free haemoglobin for degradation and iron recycling. Hpt was recently found able to bind the apolipoprotein A‐I (ApoA‐I), thus impairing its stimulation on the activity of the enzyme lecithin‐cholesterol acyl‐transferase (LCAT).

Study design  Hpt was isolated from patients with psoriasis vulgaris, and its activity in haemoglobin or ApoA‐I binding and LCAT inhibition was compared with that of normal protein.

Methods  Two affinity chromatography steps, the first using resin‐coupled haemoglobin and the second anti‐Hpt antibodies, were used to purify Hpt. The protein phenotype was assessed by electrophoresis. Binding experiments were performed by Enzyme‐linked immunosorbent assay with stationary haemoglobin or ApoA‐I, Hpt in solution and anti‐Hpt antibodies for detection of bound Hpt. Standard LCAT assays were carried out in the presence of Hpt purified from patients or healthy subjects.

Results  Phenotype prevalence of Hpt in psoriasis was not found. After affinity chromatography by haemoglobin, albumin and ApoA‐I were routinely found heavily contaminating only Hpt from normal subjects. Isolated Hpt from patients had lower activity than normal protein in both haemoglobin binding and LCAT inhibition.

Conclusions  In psoriasis, Hpt displays some structure modification(s), which might be associated with the protein function in the disease.
Multicentric Reticulohistiocytosis: A Proliferation of Macrophages With Tropism for Skin and Joints, Part II
Authors: Luz Flávio Barbosa , Gaspar Neide Kalil , Gaspar Antonio Pedro , Carneiro Sueli , Ramos‐e‐Silva Marcia
Published: September 2007

In this second part of the review of multicentric reticulohistiocytosis, the authors discuss its association with other diseases, in particular, cancer, and laboratory and therapeutic aspects of this incapacitating and disfiguring disease. Histopathologic aspects are characteristic: dense mononuclear infiltrate with typical multinucleated cells that contain periodic acid‐Schiff‐positive and diastasis‐resistant material, conferring a “ground glass” aspect when stained with hematoxylineosin
.
Sexually Transmitted Infections—Microbial Infections, 2007 Update
Authors: Waugh Michael
Published: September 2007

Human sexual behavior required for the continuation of humankind nevertheless has its downsides, among them sexually transmitted infections (STIs). The treatment of microbial STIs is challenging but not in itself essentially very difficult. Controlling STIs, on the other hand, is like the task of Sisyphus, a king in Greek mythology who was forced forever to roll a block of stone to the top of a steep hill, only to see it roll back to the valley, where he started the toilsome task again. This is how many a venereologist must view the day's practice, supervising patients with STIs. Yes, there are newcomers, many of them very young, but there are many others, the recidivists, whom the physician and health care staff know only too well. “You don't mind seeing me again, doc. You (collectively) were so good to me last time”—as though catching a chlamydial infection 3 or 4 times, gonorrhea 20 or 30 times, and syphilis on occasion were badges of virility or part of life's natural progression. This is the pattern of STIs in 2007.
Elastosis Perforans Serpiginosa
Authors: Suneja Tina , Zelonis Beth , Hurley M. Yadira , Youker Summer R.
Published: September 2007

A 41‐year‐old white man with Down syndrome presented with a slightly pruritic, papular eruption on bilateral forearms of several years' duration. Physical examination revealed multiple 2‐ to 3‐mm keratotic, umbilicated pink papules in an annular configuration distributed symmetrically on the flexural surfaces of the forearms (Figure 1). The skin surrounding these papules was noted to be hyperpigmented and somewhat atrophic. The remainder of his skin examination was unremarkable. A shave biopsy of 1 papule was performed and stained with hematoxylin‐eosin. Hematoxylin‐eosin‐stained sections showed clumps of bright red fibers being extruded through an acanthotic epidermis with a central invagination (Figure 2). Verhoeff‐van Gieson stain confirmed these fibers to be elastin (Figure 3). Elastosis perforans serpiginosa was diagnosed.

The clinical image of elastosis perforans serpiginosa is shown here.

image

A shave biopsy yielded this histologic section of elastosis perforans serpiginosa (hematoxylin‐eosin stain, original magnification ×10).

image

In this case of elastosis perforans serpiginosa, the fibers were confirmed to be elastin (elastic fibers are black) (Verhoeff‐van Gieson stain, original magnification ×20).

image
Atopic Dermatitis and Vα24+ Natural Killer T Cells
Authors: Ilhan Fulya , Kandi Basak , Akbulut Handan , Turgut Dilara , Cicek Demet
Published: September 2007

Objective.

Atopic dermatitis is a chronic inflammatory skin disease associated with cutaneous hyperreactivity to environmental triggers and is often the first step in the atopic march that results in asthma and allergic rhinitis. Helper T cells and their cytokines, in addition to IgE and eosinophils, play a major role in the pathogenesis of atopic dermatitis. Natural killer T (NKT) cells may play a role in atopic dermatitis status.

Methods.

The authors examined the percentage of Vα24+CD161+ NKT cells and CD3+CD16+ CD56+ NKT cells in peripheral blood from 23 patients with atopic dermatitis aged 8 to 35 years (mean, 21.77±2.88 years) and 30 healthy controls aged 18 to 32 years (mean, 24.32±2.44 years) by using flow cytometric analysis. The mean percentages of Vα24+CD161+ NKT cell subtypes in the atopic dermatitis group and the healthy group were 0.29%±0.02% and 0.42%±0.05%, respectively (P<.001).

Results.

Percentages of Vα24+CD161+ NKT cell subtypes are significantly lower in patients with atopic dermatitis than healthy individuals. On the other hand, the CD3+CD16+CD56+ NKT cell subtype does not differ between the groups.

Conclusions.

The reduction of Vα24+CD161+ NKT cells subtypes may be involved in the immunopathogenesis of atopic dermatitis.
Dental treatment of a 2‐year‐old victim of a suicide bomb attack
Authors: Katz‐Sagi Hadas , Gozal David , Ram Diana
Published: September 2007

Abstract –  The purpose of this report was to describe the diagnosis and dental treatment of a 2‐year‐old girl that was involved in a suicide bomb attack. A 14‐months‐old infant was severely injured when a suicide bomber detonated an explosive device inside a crowded bus. Her injury was ‘multi‐system’, mainly burns and fragments in her face, eyes and other parts of the body. Fifteen months later, she was brought to the Department of Pediatric Dentistry of the Hadassah School of Dental Medicine and the clinical and radiographic examination showed that she was caries free but there were dental trauma injuries to many teeth. Due to her non‐cooperative behavior and the extent of treatment the girl was scheduled for a one appointment treatment under deep sedation. Three days later, she was brought to the Emergency Room of the Department of Pediatric Dentistry complaining of pain on the lower left side of the mouth and a swollen vestibule and face could clinically be observed. The lower left first molar that apparently revealed only an enamel fracture and cracks at the time of treatment, actually revealed a necrotic pulp as a result of the blast. As this girl was caries free, and with no history of dental trauma due to any accident, the only explanation for the response of the pulp was the impact of the blast. In conclusion, the reaction of the dental pulp to the blast of an explosion is different than the reaction to other kind of insult and this should be taken in consideration when treating children after this kind of dental trauma.
Epitope Specificities of the Group Y and W-135 Polysaccharides ofNeisseria meningitidis
Authors: Moore Samuel L. , Uitz Catherine , Ling Chang-Chun , Bundle David R. , Fusco Peter C. , Michon Francis
Published: September 2007

Previous studies have identified the length dependency of several polysaccharide (PS) protective epitopes. We have investigated whether meningococcal polysaccharides Y and W-135 possess such epitopes. Oligosaccharides (OSs) consisting of one or more disaccharide repeating units (RU) were derived from the capsular PSs of group Y and W-135 meningococci (GYMP and GWMP, respectively) by mild acid hydrolysis. The relative affinities of anticapsular antibodies binding to derivative OSs of different chain lengths were measured in inhibition enzyme-linked immunosorbent assays. As OS size increased from two to three RU, there was a notable increase in binding inhibition of rabbit anti-group Y antiserum. This pattern of antibody binding inhibition was also observed for rabbit antiserum to group W-135, though the inhibition increase was much more pronounced. In the cases of both OS species, the concentration of inhibiting antigen required to achieve 50% inhibition of rabbit immunoglobulin binding increased progressively as the inhibiting disaccharide chain length increased from 1 RU through greater than 50 RU. These data suggest that antibodies directed against both of these meningococcal PSs recognize conformational epitopes only fully expressed in higher-molecular-weight forms of these antigens.
Comparative Evaluation of the Automated Roche TaqMan Real-Time Quantitative Human Immunodeficiency Virus Type 1 RNA PCR Assay and the Roche AMPLICOR Version 1.5 Conventional PCR Assay
Authors: Oliver Anthony R. , Pereira Spyridon F. , Clark Duncan A.
Published: September 2007

The need to evaluate antiviral treatment response and the emergence of resistance have made the human immunodeficiency virus (HIV) viral load assay a major feature of the diagnostic monitoring of HIV-infected individuals. The objective of this study was to evaluate the utility of the recently In Vitro Diagnostic Medical Devices Directive-approved Roche COBAS AmpliPrep/TaqMan96 real-time PCR assay by comparison with the existing Roche COBAS AmpliPrep/AMPLICOR MONITOR conventional PCR assay. EDTA-treated plasma samples from 191 HIV-1-infected individuals were tested for HIV-1 RNA by the AMPLICOR assay and the TaqMan assay. This was a prospective study using 191 pairs of samples from the same bleed per patient. The correlation coefficient of the assays was 98.08%. The mean difference between the assays was 0.05 log
10
copy/ml plasma, with a standard deviation (SD) of 0.27 log
10
copy/ml plasma. Thirteen samples gave results with variances greater than 0.5 log
10
copy/ml plasma, which is our clinical cutoff. Two samples were more than 3 SD different (0.81 log
10
copy/ml plasma). The TaqMan assay appeared to be slightly more sensitive at the lower end of the dynamic range. The assays correlated significantly (
P
> 0.95) with each other, and the regression analysis was also highly significant (
R
2
> 0.95).
Rapid Multiplex Nested PCR for Detection of Respiratory Viruses
Authors: Lam W. Y. , Yeung Apple C. M. , Tang Julian W. , Ip Margaret , Chan Edward W. C. , Hui Mamie , Chan Paul K. S.
Published: September 2007

Respiratory tract infections can be caused by a heterogeneous group of viruses and bacteria that produce similar clinical presentations. Specific diagnosis therefore relies on laboratory investigation. This study developed and evaluated five groups of multiplex nested PCR assays that could simultaneously detect 21 different respiratory pathogens: influenza A virus (H1N1, H3N2, and H5N1); influenza B virus; parainfluenza virus types 1, 2, 3, 4a, and 4b; respiratory syncytial virus A and B; human rhinoviruses; human enteroviruses; human coronaviruses OC43 and 229E; severe acute respiratory syndrome coronavirus; human metapneumoviruses;
Mycoplasma pneumoniae
;
Chlamydophila pneumoniae
;
Legionella pneumophila
; and adenoviruses (A to F). These multiplex nested PCRs adopted fast PCR technology. The high speed of fast PCR (within 35 min) greatly improved the efficiency of these assays. The results show that these multiplex nested PCR assays are specific and more sensitive (100- to 1,000-fold) than conventional methods. Among the 303 clinical specimens tested, the multiplex nested PCR achieved an overall positive rate of 48.5% (95% confidence interval [CI], 42.9 to 54.1%), which was significantly higher than that of virus isolation (20.1% [95% CI, 15.6 to 24.6%]) and that of direct detection by immunofluorescence assay (13.5% [95% CI, 9.7 to 17.4%]). The improved sensitivity was partly due to the higher sensitivity of multiplex nested PCR than that of conventional methods in detecting cultivatable viruses. Moreover, the ability of the multiplex nested PCR to detect noncultivatable viruses, particularly rhinoviruses, coronavirus OC43, and metapneumoviruses, contributed a major gain (15.6%) in the overall positive rate. In conclusion, rapid multiplex nested PCR assays can improve the diagnostic yield for respiratory infections to allow prompt interventive actions to be taken.
Highly Sensitive and Broadly Reactive Quantitative Reverse Transcription-PCR Assay for High-Throughput Detection of Rift Valley Fever Virus
Authors: Bird Brian H. , Bawiec Darcy A. , Ksiazek Thomas G. , Shoemaker Trevor R. , Nichol Stuart T.
Published: September 2007

Rift Valley fever (RVF) virus is a mosquito-borne virus associated with large-scale epizootics/epidemics throughout Africa and the Arabian peninsula. Virus infection can result in economically disastrous “abortion storms” and high newborn mortality in livestock. Human infections result in a flu-like illness, with 1 to 2% of patients developing severe complications, including encephalitis or hemorrhagic fever with high fatality rates. There is a critical need for a highly sensitive and specific molecular diagnostic assay capable of detecting the natural genetic spectrum of RVF viruses. We report here the establishment of a pan-RVF virus quantitative real-time reverse transcription-PCR assay with high analytical sensitivity (∼5 RNA copies of in vitro-transcribed RNA/reaction or ∼0.1 PFU of infectious virus/reaction) and efficiency (standard curve slope = −3.66). Based on the alignments of the complete genome sequences of 40 ecologically and biologically diverse virus isolates collected over 56 years (1944 to 2000), the primer and probe annealing sites targeted in this assay are known to be located in highly conserved genomic regions. The performance of this assay relative to serologic assays is illustrated by testing of known RVF case materials obtained during the Saudi Arabia outbreak in 2000. Furthermore, analysis of acute-phase blood samples collected from human patients (25 nonfatal, 8 fatal) during that outbreak revealed that patient viremia at time of presentation at hospital may be a useful prognostic tool in determining patient outcome.
Mycobacterium alsiense, a Novel, Slowly Growing Species Isolated from Two Patients with Pulmonary Disease
Authors: Richter Elvira , Tortoli Enrico , Fischer Arno , Hendricks Oliver , Engel Regina , Hillemann Doris , Schubert Sabine , Kristiansen Jette E.
Published: September 2007

A previously undescribed, slowly growingMycobacteriumspecies was isolated from pulmonary specimens of two patients, one from Denmark and one from Italy. The isolates showed unique 16S rRNA internal transcribed spacers andhsp65sequences: the 16S rRNA was most closely related toMycobacterium szulgaiandMycobacterium malmoense.
Clinical Features and Complete Genome Characterization of a Distinct Human Rhinovirus (HRV) Genetic Cluster, Probably Representing a Previously Undetected HRV Species, HRV-C, Associated with Acute Respiratory Illness in Children
Authors: Lau Susanna K. P. , Yip Cyril C. Y. , Tsoi Hoi-wah , Lee Rodney A. , So Lok-yee , Lau Yu-lung , Chan Kwok-hung , Woo Patrick C. Y. , Yuen Kwok-yung
Published: September 2007

Although human rhinoviruses (HRVs) are common causes of respiratory illness, their molecular epidemiology has been poorly investigated. Despite the recent findings of new HRV genotypes, their clinical disease spectrum and phylogenetic positions were not fully understood. In this study, 203 prospectively collected nasopharyngeal aspirates (NPAs), negative for common respiratory viruses (83 were human bocavirus [HBoV] positive and 120 HBoV negative), from hospitalized children during a 1-year period were subjected to reverse transcription-PCR for HRV. HRV was detected in 14 NPAs positive and 12 NPAs negative for HBoV. Upon VP4 gene analysis, 5 of these 26 HRV strains were found to belong to HRV-A while 21 belonged to a genetic clade probably representing a previously undetected HRV species, HRV-C, that is phylogenetically distinct from the two known HRV species, HRV-A and HRV-B. The VP4 sequences of these HRV-C strains were closely related to the newly identified HRV strains from the United States and Australia. Febrile wheeze or asthma was the most common presentation (76%) of HRV-C infection, which peaked in fall and winter. Complete genome sequencing of three HRV-C strains revealed that HRV-C represents an additional HRV species, with features distinct from HRV-A and HRV-B. Analysis of VP1 of HRV-C revealed major deletions in regions important for neutralization in other HRVs, which may be signs of a distinct species, while within-clade amino acid variation in potentially antigenic regions may indicate the existence of different serotypes among HRV-C strains. A newly identified HRV species, HRV-C, is circulating worldwide and is an important cause of febrile wheeze and asthmatic exacerbations in children requiring hospitalization.
Simultaneous Infection with More than One Strain of
Burkholderia pseudomallei
Is Uncommon in Human Melioidosis
Authors: Limmathurotsakul Direk , Wuthiekanun Vanaporn , Chantratita Narisara , Wongsuvan Gumphol , Thanwisai Aunchalee , Biaklang Mayurachat , Tumapa Sarinna , Lee Sue , Day Nicholas P. J. , Peacock Sharon J.
Published: September 2007

A prospective study was performed to determine the rate at which patients with melioidosis are infected with more than one strain of
Burkholderia pseudomallei
. Genotyping of 2,058 bacterial colonies isolated from 215 samples taken from 133 patients demonstrated that mixed infection is uncommon (2/133 cases [1.5%; 95% confidence interval, 0.2 to 5.3%]).
Interactions between Human Immunodeficiency Virus Type 1 and Vaccinia Virus in Human Lymphoid Tissue Ex Vivo
Authors: Vanpouille Christophe , Biancotto Angélique , Lisco Andrea , Brichacek Beda
Published: September 2007

Vaccinia virus (VACV) has been attracting attention recently not only as a vector for various vaccines but also as an immunization tool against smallpox because of its potential use as a bioterrorism agent. It has become evident that in spite of a long history of studies of VACV, its tissue pathogenesis remains to be fully understood. Here, we investigated the pathogenesis of VACV and its interactions with human immunodeficiency virus type 1 (HIV-1) in the context of human lymphoid tissues. We found that ex vivo-cultured tonsillar tissue supports productive infection by the New York City Board of Health strain, the VACV strain of the Dryvax vaccine. VACV readily infected both T and non-T (B) lymphocytes and depleted cells of both of these subsets equally over a 12-day period postinfection. Among T lymphocytes, CD8
+
cells are preferentially depleted in accordance with their preferential infection: the probability that a CD8
+
T cell will be productively infected is almost six times higher than for a CD4
+
T cell. T cells expressing CCR5 and the activation markers CD25, CD38, and HLA-DR are other major targets for infection by VACV in lymphoid tissue. As a consequence, VACV predominantly inhibits the replication of the R5
SF162
phenotype of HIV-1 in coinfected tissues, as R5-tropic HIV-1 requires activated CCR5
+
CD4
+
cells for productive infection. Human lymphoid tissue infected ex vivo by VACV can be used to investigate interactions of VACV with other viruses, in particular HIV-1, and to evaluate various VACV vectors for the purpose of recombinant vaccine development.
Myc and Human Papillomavirus Type 16 E7 Genes Cooperate To Immortalize Human Keratinocytes
Authors: Liu Xuefeng , Disbrow Gary L. , Yuan Hang , Tomaić Vjekoslav , Schlegel Richard
Published: September 2007

The E6 protein of the oncogenic human papillomaviruses (HPVs), in combination with the E7 protein, is essential for the efficient immortalization of human foreskin keratinocytes (HFKs). Since we recently demonstrated that E6 activates the human telomerase reverse transcriptase (hTERT) promoter via a Myc-dependent mechanism, we speculated that overexpressed Myc might be able to substitute for E6 in cell immortalization. Myc (similar to E6) was unable to immortalize HFKs when transduced alone, despite inducing high levels of telomerase activity. However, when transduced with E7, Myc immortalized HFKs following a brief but detectable crisis period. In contrast to E6 + E7-immortalized cells, the Myc + E7-immortalized cells expressed high levels of p53 protein as well as two p53-regulated proteins, p21 and hdm-2. The increase in p21 and hdm-2 proteins correlated directly with their mRNA levels, suggesting transcriptional activation of the respective genes by the overexpressed p53 protein. Interestingly, a significant proportion of the p53 protein in the Myc + E7-immortalized cells was localized to the cytoplasm, potentially due to interactions with the overexpressed hdm-2 protein. Regardless, cell immortalization by the Myc + E7 genes occurred independently of p53 degradation. Since we have already observed high-efficiency cell immortalization with the hTERT + E7 or E6 mutant (p53 degradation-defective) + E7 genes (i.e., no crisis period) that proceeds in the presence of high levels of p53, we hypothesize that the crisis period in the Myc + E7 cells is due not to the levels of the p53 protein but rather to unique properties of the Myc protein. The common factor in cell immortalization by the three gene sets (E6 + E7, Myc + E7, and hTERT + E7 genes) is the induction of telomerase activity.
Human Papillomavirus E6 Regulates the Cytoskeleton Dynamics of Keratinocytes through Targeted Degradation of p53
Authors: Cooper Brooke , Brimer Nicole , Vande Pol Scott B.
Published: September 2007

The attachment and spreading of keratinocyte cells result from interactions between integrins and immobilized extracellular matrix molecules. Human papillomavirus type 16 (HPV-16) E6 augmented the kinetics of cell spreading, while E6 genes from HPV-11 or bovine papillomavirus type 1 did not. The ability of E6 to interact with the E6AP ubiquitin ligase and target p53 degradation was required to augment cell-spreading kinetics; dominant negative p53 alleles also enhanced the kinetics of cell spreading and the level of attachment of cells to hydrophobic surfaces. The targeted degradation of p53 by E6 may contribute to the invasive phenotype exhibited by cervical cells that contain high-risk HPV types.
Herpes Simplex Virus Remodels T-Cell Receptor Signaling, Resulting in p38-Dependent Selective Synthesis of Interleukin-10
Authors: Sloan Derek D. , Jerome Keith R.
Published: September 2007

Herpes simplex virus (HSV)-specific T cells are essential for viral clearance. However, T cells do not prevent HSV latent infection or reactivation, suggesting that HSV has the potential to modulate T-cell function. T-cell receptor (TCR) stimulation is a potent and specific means of activating T cells. To investigate how HSV affects T-cell function, we have analyzed how HSV affects TCR-stimulated intracellular signaling and cytokine synthesis in mock-infected and HSV-infected T cells. Mock-infected T cells stimulated through the TCR synthesized a broad range of cytokines that included the proinflammatory cytokines tumor necrosis factor alpha, gamma interferon, and interleukin-2. In contrast, HSV-infected T cells stimulated through the TCR selectively synthesized interleukin-10, a cytokine that suppresses cellular immunity and favors viral replication. To achieve selective interleukin-10 synthesis, HSV differentially affected TCR signaling pathways. HSV inhibited TCR-stimulated formation of the linker for activation of the T-cell signaling complex, and HSV inhibited TCR-stimulated NF-κB activation. At the same time, HSV activated the p38 and JNK mitogen-activated protein kinases as well as the downstream transcription factors ATF-2 and c-Jun. HSV did not inhibit TCR-stimulated activation of STAT3, a transcription factor involved in interleukin-10 synthesis. The activation of p38 was required for interleukin-10 synthesis in HSV-infected T cells. The ability of HSV to differentially target intracellular signaling pathways and transform an activating stimulus into an immunosuppressive response represents a novel strategy for pathogen-mediated immune modulation. Selective, TCR-stimulated interleukin-10 synthesis may play an important role in HSV pathogenesis.
Activation of the Beta Interferon Promoter by Unnatural Sendai Virus Infection Requires RIG-I and Is Inhibited by Viral C Proteins
Authors: Strähle Laura , Marq Jean-Baptiste , Brini Albert , Hausmann Stéphane , Kolakofsky Daniel , Garcin Dominique
Published: September 2007

As infection with wild-type (wt) Sendai virus (SeV) normally activates beta interferon (IFN-β) very poorly, two unnatural SeV infections were used to study virus-induced IFN-β activation in mouse embryonic fibroblasts: (i) SeV-DI-H4, which is composed mostly of small, copyback defective interfering (DI) genomes and whose infection overproduces short 5′-triphosphorylated trailer RNAs (pppRNAs) and underproduces viral V and C proteins, and (ii) SeV-GFP(+/−), a coinfection that produces wt amounts of viral gene products but that also produces both green fluorescent protein (GFP) mRNA and its complement, which can form double-stranded RNA (dsRNA) with capped 5′ ends. We found that (i) virus-induced signaling to IFN-β depended predominantly on RIG-I (as opposed to mda-5) for both SeV infections, i.e., that RIG-I senses both pppRNAs and dsRNA without 5′-triphosphorylated ends, and (ii) it is the viral C protein (as opposed to V) that is primarily responsible for countering RIG-I-dependent signaling to IFN-β. Nondefective SeV that cannot specifically express C proteins not only cannot prevent the effects of transfected poly(I-C) or
ppp
RNAs on IFN-β activation but also synergistically enhances these effects. SeV-V
minus
infection, in contrast, behaves mostly like wt SeV and counteracts the effects of transfected poly(I-C) or
ppp
RNAs.
Differential Expression of Interferon (IFN) Regulatory Factors and IFN-Stimulated Genes at Early Times after West Nile Virus Infection of Mouse Embryo Fibroblasts
Authors: Scherbik Svetlana V. , Stockman Bronislava M. , Brinton Margo A.
Published: September 2007

Although lineage I West Nile virus (WNV) strain Eg101 induced beta interferon (IFN-β) production as early as 12 h after infection in primary mouse embryo fibroblasts and did not inhibit the JAK-STAT signaling pathway, it was still able to replicate efficiently. To gain insights about possible viral countermeasures used by this virus to suppress the host response, the cell transcriptional profile and the kinetics of IFN regulatory factor (IRF) expression and activation were examined at early times after infection. By 12 h after WNV infection, the majority of the up-regulated genes were ones involved in IFN pathways. However, comparison of IFN-stimulated gene (ISG) expression levels in mock-infected, IFN-treated, and virus-infected cells indicated that WNV infection suppressed the up-regulation of a subset of ISGs, including genes involved in transcriptional regulation, apoptosis, and stress responses, prior to 24 h after infection. Analysis of mRNA and protein levels for representative genes indicated that suppression was at the transcriptional and posttranscriptional levels. Translocation of IRF-3 to the nucleus was observed beginning at 8 h, IRF-7 expression was detected by 12 h, but IRF-1 expression was not detected until 24 h after infection. Virus-induced gene suppression was sufficient to overcome the effect of exogenous IFN pretreatment for 1 h but not for 4 h prior to infection. These data indicate that WNV can selectively counteract the host response at early times after infection by previously unreported mechanisms.
Effects of Identity Minimization on Moloney Murine Leukemia Virus Template Recognition and Frequent Tertiary Template-Directed Insertions during Nonhomologous Recombination
Authors: Duggal Nisha K. , Goo Leslie , King Steven R. , Telesnitsky Alice
Published: September 2007

Homology requirements for Moloney murine leukemia virus recombination were addressed in this study by monitoring titer defects observed when acceptor/donor template identity lengths were systematically reduced. Recombination acceptors with at least 16 contiguous bases of donor template identity were recognized as efficiently as longer acceptors. In contrast, a sharp 1-log titer drop was observed for an acceptor of only 15 bases long, with an additional 1-log titer decline for an 8-base acceptor and further decreases for shorter acceptors. Eighty-three independent nonhomologous recombination products were sequenced to examine recombination template selection in the absence of significant sequence identity. These replication products contained a total of 152 nonhomologous crossover junctions. Forced copy choice models predict that forced nonhomologous recombination should result in DNA synthesis to the donor template's 5′ end, followed by microidentity-guided acceptor template selection. However, only a single product displayed this structure. The majority of examined nonhomologous recombination products contained junction-associated sequence insertions. Most insertions resulted from the use of one or more tertiary templates, recognizable as discontiguous portions of viral or host RNA or minus-strand DNA. The donor/acceptor template microidentity evident at most crossovers reconfirmed the remarkable capability of the reverse transcription machinery to recognize short regions of sequence identity. These results demonstrate that recruitment of discontiguous host or viral sequences is a common way for retroviruses to resolve nonhomologous recombination junctions and provide experimental support for the role of splinting templates in the generation of retroviral insertions.
Hepatitis C Virus Infection Induces the Beta Interferon Signaling Pathway in Immortalized Human Hepatocytes
Authors: Kanda Tatsuo , Steele Robert , Ray Ranjit , Ray Ratna B.
Published: September 2007

Beta interferon (IFN-β) expression is triggered by double-stranded RNA, a common intermediate in the replication of many viruses including hepatitis C virus (HCV). The recent development of cell culture-grown HCV allowed us to analyze the IFN signaling pathway following virus infection. In this study, we have examined the IFN-β signaling pathway following infection of immortalized human hepatocytes (IHH) with HCV genotype 1a (clone H77) or 2a (clone JFH1). We observed that IHH possesses a functional Toll-like receptor 3 pathway. HCV infection in IHH enhanced IFN-β and IFN-stimulated gene 56 (ISG56) promoter activities; however, poly(I-C)-induced IFN-β and ISG56 expression levels were modestly inhibited upon HCV infection. IHH infected with HCV (genotype 1a or 2a) exhibited various levels of translocation of IRF-3 into the nucleus. The upregulation of endogenous IFN-β and 2′,5′-oligoadenylate synthetase 1 mRNA expression was also observed in HCV-infected IHH. Subsequent studies suggested that HCV infection in IHH enhanced STAT1 and ISG56 protein expression. A functional antiviral response of HCV-infected IHH was observed by the growth-inhibitory role in vesicular stomatitis virus. Together, our results suggested that HCV infection in IHH induces the IFN signaling pathway, which corroborates observations from natural HCV infection in humans.
Inhibition of Human Immunodeficiency Virus Type 1 Concerted Integration by Strand Transfer Inhibitors Which Recognize a Transient Structural Intermediate
Authors: Pandey Krishan K. , Bera Sibes , Zahm Jacob , Vora Ajaykumar , Stillmock Kara , Hazuda Daria , Grandgenett Duane P.
Published: September 2007

Human immunodeficiency virus type 1 (HIV-1) integrase (IN) inserts the viral DNA genome into host chromosomes. Here, by native agarose gel electrophoresis, using recombinant IN with a blunt-ended viral DNA substrate, we identified the synaptic complex (SC), a transient early intermediate in the integration pathway. The SC consists of two donor ends juxtaposed by IN noncovalently. The DNA ends within the SC were minimally processed (∼15%). In a time-dependent manner, the SC associated with target DNA and progressed to the strand transfer complex (STC), the nucleoprotein product of concerted integration. In the STC, the two viral DNA ends are covalently attached to target and remain associated with IN. The diketo acid inhibitors and their analogs effectively inhibit HIV-1 replication by preventing integration in vivo. Strand transfer inhibitors L-870,810, L-870,812, and L-841,411, at low nM concentrations, effectively inhibited the concerted integration of viral DNA donor in vitro. The inhibitors, in a concentration-dependent manner, bound to IN within the SC and thereby blocked the docking onto target DNA, which thus prevented the formation of the STC. Although 3′-OH recessed donor efficiently formed the STC, reactions proceeding with this substrate exhibited marked resistance to the presence of inhibitor, requiring significantly higher concentrations for effective inhibition of all strand transfer products. These results suggest that binding of inhibitor to the SC occurs prior to, during, or immediately after 3′-OH processing. It follows that the IN-viral DNA complex is “trapped” by the strand transfer inhibitors via a transient intermediate within the cytoplasmic preintegration complex.
The self-archiving principle: a momentous trek
Authors: Singh Nishith K
Published: September 2007

In the existing scholarly publishing empire, authors give away their valued research work to various commercial journals, thereby restricting free accessibility to the published useful work. Triggered by the gargantuan promise of the internet, the self-archiving principle is a new and revolutionary concept which potentially lets all research work become freely available online. It involves deposition of research documents at a publicly accessible website, and its proponents see the initiative as a means to set entire author works free of all access and impact barriers. This review briefly discusses the allied concepts, the course and implications of the initiative.
Orthostatic hypotension: framework of the syndrome
Authors: Naschitz Jochanan E , Rosner Itzhak
Published: September 2007

According to the 1996 consensus definition, orthostatic hypotension (OH) is diagnosed when a fall in systolic blood pressure of at least 20 mm Hg and/or diastolic blood pressure of at least 10 mm Hg within 3 min of standing is recorded. The elements of orthostatic blood pressure drop that are relevant to the definition of OH include magnitude of the drop, time to reach the blood pressure difference defined as OH, and reproducibility of the orthostatic blood pressure drop. In each of these elements, there exist issues that argue for modification of the presently accepted criteria of OH. Additional questions need to be addressed. Should one standard orthostatic test be applied to different patient populations or should tests be tailored to the patients' clinical circumstances? Are different OH thresholds relevant to various clinical settings, aetiologies of OH and comorbidity? Which test has the best predictive power of morbidity and mortality?
A national online survey of final year medical students' opinion on the General Medical Council's proposed reforms to the undergraduate medical assessment system
Authors: Khan Kamran Z , Sear John W
Published: September 2007

Background

The General Medical Council (GMC) is holding consultations in order to decide on the proposed changes to the undergraduate medical assessment. In the last round of consultation only eight medical students formally responded nationally.

Aim

To determine the views of a larger proportion of final year medical students across the country on the proposed changes to the undergraduate medical assessment.

Method

An online national survey of 10 medical schools, from which 401 responses from final year medical students were collected.

Results and discussion

The results indicate the medical students' views on the GMC's proposed changes to standardise the assessment system. The majority of the students were in favour of having a say in any changes to their future assessment. They agreed with the principle that there should be a consistency between assessments at different medical schools and currently their results did not represent preparedness to practice.
Heparin induced thrombocytopenia: diagnosis and management update
Authors: Ahmed I , Majeed A , Powell R
Published: September 2007

Heparin-induced thrombocytopenia (HIT) is a potentially devastating immune mediated adverse drug reaction caused by the emergence of antibodies that activate platelets in the presence of heparin. Despite thrombocytopenia, bleeding is rare; rather, HIT is strongly associated with thromboembolic complications involving both the arterial and venous systems. A number of laboratory tests are available to confirm the diagnosis; however, when HIT is clinically suspected, treatment should not be withheld pending the result. Fortunately, therapeutic strategies have been refined, and new and effective therapeutic agents are available. Treatment options are focused on inhibiting thrombin formation or direct thrombin inhibition. Warfarin should not be used until the platelet count has recovered.
The role of genetics in stroke
Authors: Francis John , Raghunathan Senthil , Khanna Pradeep
Published: September 2007

Stroke is a leading cause of death and disability in developed countries. While both modifiable and non-modifiable risk factors are acknowledged, studies have shown that these may account for just 50% of stroke risk and that other factors, including genetic ones, may be important. Over recent years family history, twin and candidate gene studies have supported this and various mendelian stroke syndromes have now been identified in humans. This article provides an up-to-date summary of the common single gene disorders associated with stroke as a principle manifestation, including their genetic basis, pathogenesis, presentation and suggested management. Often these disorders present with stroke at a young age; this article provides a practical approach to the management and investigation of a young stroke patient.
A cross sectional survey of secondary prevention measures in patients with peripheral arterial disease in primary care
Authors: Dunkley Alison , Stone Margaret , Sayers Robert , Farooqi Azhar , Khunti Kamlesh
Published: September 2007

Background

The National Service Framework for coronary heart disease (CHD) defines standards for the secondary prevention of cardiovascular disease in at risk individuals, including those with peripheral arterial disease (PAD).

Aim

To assess current standards of secondary prevention and health monitoring in patients with PAD following a vascular procedure, and additionally compare care in patients with and without diagnosed CHD.

Methods

Indicators for this cross sectional survey were identified from national recommendations and evidence. A retrospective review was conducted of general practitioner records, for patients who were treated in hospital for PAD.

Results

Data were collected for 103 patients from 42 practices. Overall, prescribing was well achieved for antiplatelets but poor for statins. Standards of assessment of blood pressure, smoking status, and smoking cessation advice were high. However, approximately only half of the patients received advice about exercise or had their body mass index checked. Furthermore, for all indicators, standards of care for patients who additionally had a diagnosis of CHD were better than for patients without CHD.

Conclusion

The cross sectional survey suggested the treatment received by some patients with established PAD is substandard. There is considerable potential to increase secondary prevention of CHD in patients with PAD disease in primary care.
Prolactin is an important regulator of intestinal calcium transport
Authors: Charoenphandhu Narattaphol , Krishnamra Nateetip
Published: September 2007

Prolactin has been shown to stimulate intestinal calcium absorption, increase bone turnover, and reduce renal calcium excretion. The small intestine, which is the sole organ supplying new calcium to the body, intensely expresses mRNAs and proteins of prolactin receptors, especially in the duodenum and jejunum, indicating the intestine as a target tissue of prolactin. A number of investigations show that prolactin is able to stimulate the intestinal calcium transport both in vitro and in vivo, whereas bromocriptine, which inhibits pituitary prolactin secretion, antagonizes its actions. In female rats, acute and long-term exposure to high prolactin levels significantly enhances the (i) transcellular active, (ii) solvent drag-induced, and (iii) passive calcium transport occurring in the small intestine. These effects are seen not only in pregnant and lactating animals, but are also observed in non-pregnant and non-lactating animals. Interestingly, young animals are more responsive to prolactin than adults. Prolactin-enhanced calcium absorption gradually diminishes with age, thus suggesting it has an age-dependent mode of action. Although prolactin's effects on calcium absorption are not directly vitamin D-dependent; a certain level of circulating vitamin D may be required for the basal expression of genes related to calcium transport. The aforementioned body of evidence supports the hypothesis that prolactin acts as a regulator of calcium homeostasis by controlling the intestinal calcium absorption. Cellular and molecular signal transductions of prolactin in the enterocytes are largely unknown, however, and still require investigation.
Effect of pioglitazone and its combination with statins in coronary artery disease patients with hyperinsulinemia
Authors: Mehta Anita , Shah Urmil , Parikh Keyur , Chag Milan , Baxi Hemang , Chandarana Anish , Naik Ajay , Naik Asha , Shah Kanan , Goyal Ramesh
Published: September 2007

The objective of the study was to demonstrate the effect of pioglitazone and pioglitazone in combination with statin on East Indian patients with hyperinsulinemia and hyperlipidemia. It was a randomized, placebo-controlled, double-blind study with a parallel-group design comprising 83 patients. Patients of either sex with cardiac complications, including hyperlipidemia and (or) diabetes mellitus with or without hyperinsulinemia, were enrolled. Patients over 70 years of age, with renal or hepatic failure, or with severe diabetes mellitus (total glucose >400 mg/dL) were excluded from the study. Enrolled patients were randomly assigned to 4 groups that received placebo, pioglitazone, atorvastatin, or both. Blood samples were collected before and after treatment for analysis of serum glucose, insulin, lipid profile, apolipoprotein (apo) A1, apo B, and fibrinogen. Data were compared with that of patients with normal insulin or hyperinsulinemia. The patients with hyperinsulinemia receiving only pioglitazone showed a significant decrease in insulin levels compared with those with normal insulin levels. These patients also showed a significant increase in HDL levels. However, no significant change was observed in patients treated with both atorvastatin and pioglitazone. Pioglitazone was also found to increase significantly the apo A1 levels in patients with hyperinsulinemia, but there was no significant increase in patients given both atorvastatin and pioglitazone. Our data suggests that pioglitazone should be given preferably to the patients with hyperinsulinemia and statin should not be coadministered.
Hypolipidemic and antioxidant effects of curcumin and capsaicin in high-fat-fed rats
Authors: Manjunatha H. , Srinivasan K.
Published: September 2007

The beneficial hypolipidemic and antioxidant influences of the dietary spice compounds curcumin and capsaicin were evaluated. Curcumin, capsaicin, or their combination were included in the diet of high-(30%)-fat-fed rats for 8 weeks. Dietary high-fat-induced hypertriglyceridemia was countered by dietary curcumin, capsaicin, or their combination by 12%–20%. Curcumin, capsaicin, and their combination also produced a slight decrease in serum total cholesterol in these animals. Serum α-tocopherol content was increased by dietary curcumin, capsaicin, and their combination in high-fat-fed rats. Serum total thiol content in high-fat-fed animals and serum ascorbic acid in normal animals was elevated by the combination of curcumin and capsaicin. Hepatic glutathione was increased by curcumin, capsaicin, or their combination in normal animals. Hepatic glutathione and α-tocopherol were increased, whereas lipid peroxide level was reduced by dietary curcumin and combination of curcumin and capsaicin in high-fat-fed animals. Serum glutathione peroxidase and glutathione transferase in high-fat-fed rats were generally higher as a result of dietary curcumin, capsaicin, and the combination of curcumin and capsaicin. Hepatic glutathione reductase and glutathione peroxidase were significantly elevated by dietary spice principles in high-fat-fed animals. The additive effect of the 2 bioactive compounds was generally not evident with respect to hypolipidemic or antioxidant potential. However, the effectiveness of the combination was higher in a few instances.