ADDICTION, Issue 3 2006
Colette Smit
ABSTRACT Aims To study sexual risk and injecting behaviour among HIV-infected drug users (DU) receiving highly active antiretroviral therapy (HAART)., Design and setting As part of an ongoing prospective cohort study, HIV-infected DU who commenced HAART (n = 67) were matched with those not starting HAART (n = 130) on CD4 cell counts, duration of cohort participation, age and calendar year of visit. Immunological and virological responses of the HAART-treated DU were compared with the HAART-treated homosexual men from the same cohort (n = 212). Measurements Trends in behaviour and therapeutic response were tested with a logistic regression model adjusted for repeated measurements and a piecewise random effects model, respectively. Findings Non-HAART users reported more episodes of injecting than HAART users. In both groups injecting declined over time with no effect of HAART initiation. Before HAART initiation an increase in sexual risk behaviour was observed among those who had been assigned to receive HAART; their sexual risk behaviour declined thereafter. No change in sexual risk behaviour was found among non-HAART users. Relative to homosexual men, DU had a similar initial therapeutic response, but DU started HAART at lower CD4 cell counts and higher viral load levels. Conclusion DU who are treated with HAART are not increasing their risk behaviour, and their early response to HAART is similar to homosexual men. However, before the treated DU received HAART they were seen to inject less often than those not treated with HAART. This suggests that selection of potential HAART starters is based on limited drug use. Although the DU who commence HAART are a selected group, our results show that HIV-infected DU can be treated effectively. [source]

Prednisolone Priming Enhances Th1 Response and Efficacy of Subsequent Lamivudine Therapy in Patients With Chronic Hepatitis B

HEPATOLOGY, Issue 3 2000
Yun-Fan Liaw M.D.
Asian lamivudine trial has shown that hepatitis B e antigen (HBeAg) seroconversion rate during 1 year of lamivudine therapy was only 16% but was 64% in the subgroup of patients with a pretherapy serum alanine transaminase (ALT) level over 5 times the upper limit of normal (ULN). To test whether ALT rebound following corticosteroid priming enhances response to lamivudine therapy, a pilot study was conducted in 30 patients with ALT levels less than 5× ULN (43-169; N < 36 U/L). They received 30 mg of prednisolone daily for 3 weeks, 15 mg daily for 1 week, no treatment for 2 weeks, and then 150 mg of lamivudine daily for 9 months. Complete response (CR) was defined as ALT normalization with HBV-DNA seroclearance and HBeAg seroconversion. Peripheral blood mononuclear cell proliferation and cytokine secretion in response to recombinant HBV core antigen were serially assayed in 7 patients during priming and after withdrawal of prednisolone. Clinical rebound with an ALT over 5× ULN was observed in 20 patients (67%). Of these 20, 12 (60%) showed CR as compared with 1 (10%) of the 10 patients without significant ALT rebound (P < .002). The HBeAg seroconversion sustained in 70% of the patients 3 to 6 months after the end of lamivudine therapy. Immunological assays revealed that the responders showed Th1 dominant response and higher stimulation index to prednisolone priming. No serious side effect was encountered. These results suggest that corticosteroid priming induced immune/ALT rebound greatly enhances response to lamivudine therapy in chronic hepatitis B. Confirmation by randomized controlled trial is needed. [source]

Mitochondrial transport proteins of the brain

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 15 2007
D.A. Berkich
Abstract In this study, cellular distribution and activity of glutamate and ,-aminobutyric acid (GABA) transport as well as oxoglutarate transport across brain mitochondrial membranes were investigated. A goal was to establish cell-type-specific expression of key transporters and enzymes involved in neurotransmitter metabolism in order to estimate neurotransmitter and metabolite traffic between neurons and astrocytes. Two methods were used to isolate brain mitochondria. One method excludes synaptosomes and the organelles may therefore be enriched in astrocytic mitochondria. The other method isolates mitochondria derived from all regions of the brain. Immunological and enzymatic methods were used to measure enzymes and carriers in the different preparations, in addition to studying transport kinetics. Immunohistochemistry was also employed using brain slices to confirm cell type specificity of enzymes and carriers. The data suggest that the aspartate/glutamate carriers (AGC) are expressed predominantly in neurons, not astrocytes, and that one of two glutamate/hydroxyl carriers is expressed predominantly in astrocytes. The GABA carrier and the oxoglutarate carrier appear to be equally distributed in astrocytes and neurons. As expected, pyruvate carboxylase and branched-chain aminotransferase were predominantly astrocytic. Insofar as the aspartate/glutamate exchange carriers are required for the malate/aspartate shuttle and for reoxidation of cytosolic NADH, the data suggest a compartmentation of glucose metabolism in which astrocytes catalyze glycolytic conversion of glucose to lactate, whereas neurons are capable of oxidizing both lactate and glucose to CO2 + H2O. © 2007 Wiley-Liss, Inc. [source]

Nerve growth factor mediates steroid-resistant inflammation in respiratory syncytial virus infection,,

PEDIATRIC PULMONOLOGY, Issue 6 2007
Lida Mohtasham MD
Abstract Neurotrophic factors and receptors are upregulated in the respiratory tract of humans and rodents infected by the respiratory syncytial virus, leading to airway inflammation and hyperreactivity. The contribution of neurotrophic pathways to the recruitment of immuno-inflammatory cells and their response to anti-inflammatory therapy remains unclear. We sought to determine whether selective nerve growth factor inhibition prevents the immuno-inflammatory response against infection, and explored the effect of inhaled corticosteroids on virus-induced neurotrophic upregulation and the consequent recruitment of immuno-inflammatory cells into the airways. We tried to inhibit the recruitment of lymphocytes and monocytes into the airways of infected weanling rats using immunologic inhibition of nerve growth factor with a specific blocking antibody, or chemical inhibition of receptor tyrosine kinase with K252a. The anti-inflammatory activity of inhaled corticosteroids was studied in infected rats treated with budesonide, fluticasone, or vehicle. Immunological or chemical inhibition of nerve growth factor or its high-affinity receptor tyrosine kinase pathway inhibited the recruitment of inflammatory cells triggered by nociceptive irritation of infected rat airways, thereby reducing local and systemic immuno-inflammatory responses against the virus. Neurotrophic upregulation in infected airways was not affected by inhaled corticosteroids. As a logical consequence, these commonly used drugs were also unable to stop the recruitment of immune and inflammatory effector cells into infected airways. Overexpression of neurotrophic factors and receptors in airways infected by respiratory syncytial virus is critical for the development of airway inflammation and hyperreactivity, which is resistant to the anti-inflammatory effect of inhaled corticosteroids. Pediatr Pulmonol. 2007; 42:496,504. © 2007 Wiley-Liss, Inc. [source]

Immunological and inflammatory mechanisms in ocular allergy with special reference to vernal keratoconjunctivitis.

ACTA OPHTHALMOLOGICA, Issue 2 2001
Clinical, experimental studies
No abstract is available for this article. [source]

Bridging the gap between adult and paediatric outcomes in HIV-1 vertically infected children: a single-centre comparison with adult data

ACTA PAEDIATRICA, Issue 11 2009
F Monpoux
Abstract Prognosis of HIV-1 infection dramatically improved during the last decade. Meanwhile, treatment-induced virological success has always been different in adult and children patients. Aim:, To compare 10 years of follow up in HIV-1 vertically infected children and adult patients. Methods:, Monocentric retrospective longitudinal analysis of vertically HIV-1-infected children and adult patients followed in the Nice University Hospital between 1999 and 2008. Immunological, virological and antiretroviral treatment data were recorded. Results:, Forty children and 1752 adult patients were included. Between 1996 and 2008, the percentage of children receiving HAART increased from 3.2% to 91%. Mean CD4% in the paediatric group remained stable between 29 ± 8.1% in 1998 and 30 ± 9.4% in 2008. Mean adult CD4-cell count significantly increased from 410 in 1998 to 556 cells/mL in 2008. Logistic regression analysis showed that the children-to-adult difference for indetectability (HIV PCR-RNA below 400 copies/mL) was significant (p < 0.0001) with an odds ratio of 0.61 (CI95th: 0.52,0.72). Year-to-patient interaction was also significant with a decreasing divergence over time (p: 0.038). Conclusion:, Nowadays as in adult patients, the control of HIV-1 replication is achieved in nearly eight of 10 children and the percentage of patients with severe immunodeficiency dramatically decreased compared with the mid 1990s. [source]

Close association of CD8+/CD38bright with HIV-1 replication and complex relationship with CD4+ T-cell count,

CYTOMETRY, Issue 4 2009
Edouard Tuaillon
Abstract Background: Measuring lymphocyte activation provides information in addition to CD4+ T-cell count for immune monitoring of HIV-1 infected patients. CD38 is a well-established activation marker that is generally analyzed on the whole population of CD8+ T-cells. Focusing specifically on CD38 high expression (CD8+/CD38bright) may be an interesting surrogate gating strategy because CD38bright characterizes principally activated memory cells. Methods: CD8+/CD38bright was investigated in 1,353 HIV-1 infected patients over a one-year period to establish relevant cutoff values and clarify the relationships of this marker with HIV-1 RNA viral load (VL) and CD4+ T-cell count. Results: The CD8+/CD38bright (>8,500 CD38 binding site per cells) is well correlated with HIV-1 VL (r = 0.87, P < 0.001) in this longitudinal follow-up of nonimmunodepressed patients that initiated antiviral therapy (ART). In aviremic patients on ART, the marker was highly predictive of VL rebound (sensitivity 93%, specificity 64% for a VL level of detection >200 copies/ml). While the CD8+/CD38bright moderately correlated with CD4+ T-cell count independently of the VL (r = ,0.37, P < 0.001), it increased dramatically in aviremic patient groups that exhibited profound CD4+ T-cell depletion (median 39% for CD4+ T-cell counts <50/mm3). This result indicates that other additional immunological and/or viral factors than readily detectable HIV-1 replication appears to be involved in T-cell activation of immunodepressed individuals. Conclusions: CD8+/CD38bright is an effective marker for monitoring T-cell activation, which is a central factor of HIV-1 pathogenesis. This gating strategy requires only a single additional staining in conventional four color CD4 protocols. © 2008 Clinical Cytometry Society [source]

Neurodevelopmental outcomes in children with HIV infection under 3 years of age

DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 8 2006
C J Foster BA MBBS MRCPCH
Following the introduction of combination antiretroviral therapy, children vertically infected with the human immunodeficiency virus (HIV-1) living in the developed world are surviving into adult life. This paper reviews the neurodevelopmental outcomes of 62 consecutively-presenting children with HIV-1 infection diagnosed before 3 years of age (32 males, 30 females; median age at presentation 6mo). Neurological and developmental data are presented with immunological and virological responses to antiretroviral therapy. Fourteen children (22%) had abnormal neurological signs and 25 (40%) demonstrated significant developmental delay on standardized developmental assessments. Children presenting with more severe HIV-1 disease and immune compromise had significantly more abnormal neurological signs and developmental delays than children presenting with milder HIV-1 symptomatology. Immune function, control of HIV-1 viral replication, and growth parameters improved with antiretroviral therapy (median age at last follow-up 7y 3mo); however, abnormal neurological signs and significant gross motor difficulties persisted. [source]

The biotin-streptavidin interaction can be reversibly broken using water at elevated temperatures

ELECTROPHORESIS, Issue 3 2005
Anders Holmberg
Abstract The biotin-streptavidin system is the strongest noncovalent biological interaction known, having a dissociation constant, Kd, in the order of 4×10,14 M. The strength and specificity of the interaction has led it to be one of the most widely used affinity pairs in molecular, immunological, and cellular assays. However, it has previously been impossible to re-use any streptavidin solid support, since the conditions needed to break the interaction with biotin has led to the denaturation of the streptavidin. Here, we show that a short incubation in nonionic aqueous solutions at temperatures above 70°C can efficiently break the interaction without denaturing the streptavidin tetramer. Both biotin and the streptavidin remain active after dissociation and both molecules can therefore be re-used. The efficiency of the regeneration allowed solid supports with streptavidin to be used many times, here exemplified with the multiple re-use of streptavidin beads used for sample preparation prior to automated DNA sequencing. The results suggest that streptavidin regeneration can be introduced as an improvement in existing methods and assays based on the streptavidin system as well as emerging solid phase applications in fields, such as microfluidics and nanotechnology. [source]

Genetic, immunological and biochemical evidence for a Rnf complex in the acetogen Acetobacterium woodii

ENVIRONMENTAL MICROBIOLOGY, Issue 6 2009
Eva Biegel
Summary Acetogenic bacteria grow by the oxidation of various substrates coupled to the reduction of carbon dioxide (acetogenesis) or other electron acceptors but the mechanisms of energy conservation are still enigmatic. Here, we report the presence of a rnf gene cluster rnfCDGEAB in Acetobacterium woodii that is speculated to encode a novel, energy-conserving ferredoxin:NAD+ -oxidoreductase complex composed of at least six different subunits. Transcriptional analysis revealed that the genes constitute an operon. RnfC and RnfG were heterologously produced and antibodies were generated. Western blot analyses demonstrated that these subunits were produced and are associated with the cytoplasmic membrane. The subunits were present in cells respiring with either carbon dioxide or caffeate. A preparation with NADH dehydrogenase activity was obtained from detergent solubilized membranes that contained RnfC and RnfG. [source]

Malondialdehyde modification of myelin oligodendrocyte glycoprotein leads to increased immunogenicity and encephalitogenicity

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2007
Maja Wållberg
Abstract Self proteins may become autoantigenic through structural modification. We studied malondialdehydation of recombinant rat (rr) myelin oligodendrocyte glycoprotein (MOG), an autoantigen in multiple sclerosis. Malondialdehyde (MDA) modification changed protein weight and charge, the location of these adducts being mapped by Fourier transform ion cyclotron resonance. Molecular modelling revealed significant differences in the MDA-rrMOG three-dimensional structure. DBA/1 mice immunised with MDA-rrMOG developed greater proliferative responses and more severe experimental autoimmune encephalomyelitis than mice immunised with unmodified rrMOG. MDA-rrMOG was taken up more effectively by antigen-presenting cells (APC), at least partially through scavenger receptors. Exposure to MDA-rrMOG led to increased expression of IL-23, IL-12 and IL-12R, indicating a role not only for increased antigen uptake but also for activation of APC. We thus provide biochemical, structural, immunological and clinical data that suggest that the post-translationally modified form of this myelin autoantigen is a more relevant form of the molecule. [source]

A reversibly immortalized human hepatocyte cell line as a source of hepatocyte-based biological support

ADDICTION BIOLOGY, Issue 4 2001
Naoya Kobayashi
The application of hepatocyte transplantation (HTX) is increasingly envisioned for temporary metabolic support during acute liver failure and provision of specific liver functions in inherited liver-based metabolic diseases. Compared with whole liver transplantation, HTX is a technically simple procedure and hepatocytes can be cryopreserved for future use. A major limitation of this form of therapy in humans is the worldwide shortage of human livers for isolating an adequate number of transplantable human hepatocyes when needed. Furthermore, the numbers of donor livers available for hepatocyte isolation is limited by competition for their use in whole organ transplantation. Considering the cost of hepatocyte isolation and the need for immediate preparation of consistent and functional cells, it is unlikely that human hepatocytes can be obtained on such a scale to treat a large number of patients with falling liver functions. The utilization of xenogenic hepatocytes will result in additional concerns regarding transmission of infectious pathogens and immunological and physiological incompatibilities between animals and humans. An attractive alternative to primary human hepatocytes is the use of tightly regulated human hepatocyte cell lines. Such cell lines can provide the advantages of unlimited availability, sterility and uniformity. We describe here methods for creating transplantable human hepatocyte cell lines using currently available cell cultures and gene transfer technology. [source]

Multiple sclerosis complexity in selected populations: the challenge of Sardinia, insular Italy1

EUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2002
S. Sotgiu
Several lines of evidence indicate a genetic contribution to multiple sclerosis (MS) both in terms of predisposition to the disease and of immunological mechanisms which are known to play crucial roles in MS pathogenesis. The presence of high- and low-risk areas for MS in neighbouring regions supports the theory that MS predisposition is influenced by a complex interaction of genetic and environmental factors. Therefore, the use of genetically homogeneous and geographically isolated populations becomes an increasing requirement to reduce biasing biological variables. Sardinians fulfil these conditions well because of their different phylogeny from Europeans and the unique selective pressures which shaped their genome. Sardinians display amongst the highest MS prevalence rates world-wide and increasing MS incidence rates over time. Also, MS in Sardinia is linked to distinct human leucocyte antigen (HLA) alleles and associated to different patterns of cytokine production from lymphoid cells of different HLA subtypes. In this context, recent findings and future perspectives on the peculiarities of Sardinian MS concerning genetic, immunological and epidemiological aspects are presented. So far, our results indicate that variations at the level of territorial distribution and HLA-association are present which render MS heterogeneous even in this ethnically homogeneous population. [source]

Migraine With Aura After Intracranial Endovascular Procedures

HEADACHE, Issue 4 2001
R. Beekman MD
Objective.,To describe three cases of migraine (two with aura) after an intracranial endovascular procedure. Method.,Retrospective. Results.,One patient had an attack of migraine with prolonged aura after embolization of a dural arteriovenous fistula. Another patient had an attack of migraine with aura (and hemiparesis) after a diagnostic angiogram. The third patient already suffered from migraine with aura and had a migraine attack after embolization of an occipital arteriovenous malformation. A quadrantanopia persisted in this patient. Outcome of the other two patients was good. Conclusion.,Intracranial endovascular procedures can induce migraine with aura. We could not identify the underlying pathophysiological mechanism, but mechanical, chemical, immunological, or hemodynamic factors could be involved. [source]

Prevalence of drug resistance and importance of viral load measurements in Honduran HIV-infected patients failing antiretroviral treatment

HIV MEDICINE, Issue 2 2010
W Murillo
Objective The Honduran HIV/AIDS Program began to scale up access to HIV therapy in 2002. Up to May 2008, more than 6000 patients received combination antiretroviral therapy (cART). As HIV drug resistance is the major obstacle for effective treatment, the purpose of this study was to assess the prevalence of antiretroviral drug resistance in Honduran HIV-1-infected individuals. Methods We collected samples from 138 individuals (97 adults and 41 children) on cART with virological, immunological or clinical signs of treatment failure. HIV-1 pol sequences were obtained using an in-house method. Resistance mutations were identified according to the 2007 International AIDS Society (IAS)-USA list and predicted susceptibility to cART was scored using the anrs algorithm. Results Resistance mutations were detected in 112 patients (81%), 74% in adults and 98% in children. Triple-, dual- and single-class drug resistance was documented in 27%, 43% and 11% of the study subjects, respectively. Multiple logistic regression showed that resistance was independently associated with type of treatment failure [virological failure (odds ratio (OR)=1) vs. immunological failure (OR=0.11; 95% confidence interval (CI) 0.030,0.43) vs. clinical failure (OR=0.037; 95% CI 0.0063,0.22)], route of transmission (OR=42.8; 95% CI 3.73,491), and years on therapy (OR=1.81; 95% CI 1.11,2.93). Conclusion The prevalence of antiretroviral resistance was high in Honduran HIV-infected patients with signs of treatment failure. A majority of study subjects showed dual- or triple-class resistance to nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors and protease inhibitors. Virologically defined treatment failure was a strong predictor of resistance, indicating that viral load testing is needed to correctly identify patients with treatment failure attributable to resistance. [source]

Hepatitis B or hepatitis C coinfection in HIV-infected pregnant women in Europe

HIV MEDICINE, Issue 7 2008
M Landes
Objectives The aim of the study was to investigate the prevalence of and risk factors for hepatitis C or B virus (HCV or HBV) coinfection among HIV-infected pregnant women, and to investigate their immunological and virological characteristics and antiretroviral therapy use. Methods Information on HBV surface antigen (HBsAg) positivity and HCV antibody (anti-HCV) was collected retrospectively from the antenatal records of HIV-infected women enrolled in the European Collaborative Study and linked to prospectively collected data. Results Of 1050 women, 4.9% [95% confidence interval (CI) 3.6,6.3] were HBsAg positive and 12.3% (95% CI 10.4,14.4) had anti-HCV antibody. Women with an injecting drug use(r) (IDU) history had the highest HCV-seropositivity prevalence (28%; 95% CI 22.8,35.7). Risk factors for HCV seropositivity included IDU history [adjusted odds ratio (AOR) 2.92; 95% CI 1.86,4.58], age (for ,35 years vs. <25 years, AOR 3.45; 95% CI 1.66,7.20) and HBsAg carriage (AOR 5.80; 95% CI 2.78,12.1). HBsAg positivity was associated with African origin (AOR 2.74; 95% CI 1.20,6.26) and HCV seropositivity (AOR 6.44; 95% CI 3.08,13.5). Highly active antiretroviral therapy (HAART) use was less likely in HIV/HCV-seropositive than in HIV-monoinfected women (AOR 0.34; 95% CI 0.20,0.58). HCV seropositivity was associated with a higher adjusted HIV RNA level (+0.28log10 HIV-1 RNA copies/mL vs. HIV-monoinfected women; P=0.03). HIV/HCV-seropositive women were twice as likely to have detectable HIV in the third trimester/delivery as HIV-monoinfected women (AOR 1.95; P=0.049). Conclusions Although HCV serostatus impacted on HAART use, the association between HCV seropositivity and uncontrolled HIV viraemia in late pregnancy was independent of HAART. [source]

Improved virological response to highly active antiretroviral therapy in HIV-1-infected patients carrying the CCR5 ,32 deletion

HIV MEDICINE, Issue 4 2007
JJ Laurichesse
Background Patients heterozygous for the C-C chemokine receptor 5 (CCR5) ,32 deletion spontaneously progress less rapidly to AIDS and death than do wild-type patients. We investigated whether the CCR5 ,32 deletion has an impact on immunological, virological and clinical responses to highly active antiretroviral therapy (HAART) in HIV-1-infected patients. Patients and methods We included in the study 565 HIV-1-infected patients from the French HIV-1 infected cohort with documented date of serconversion (SEROCO)/haemophiliacs HIV-1 infected (HEMOCO) cohorts, who started HAART after 1996. We investigated virological responses to HAART at 6 months (defined as a plasma HIV-1 RNA measurement below the threshold of detection or a 2 log HIV-1 RNA decrease) and at 12 months (defined as a plasma HIV-1 RNA measurement below the threshold of detection) and clinical response to HAART by Kaplan,Meier survival curves, with AIDS and death as outcomes. Results The ,32 heterozygous patients (n=83; 15%) had a better virological response to HAART than wild-type patients (73 vs 53% at 6 months, P=0.01; and 60 vs 44% at 12 months, P=0.01). This better virological response was still observed after adjustment for antiretroviral status (whether or not patients were naïve to antiretroviral therapy), year of HAART initiation, number of new antiretroviral drugs and baseline viral load. There was no statistical difference between heterozygous patients and wild-type patients in terms of survival and AIDS-free survival. Conclusions CCR5 ,32 heterozygous patients were more likely to have a virological response to HAART than wild-type patients at 6 and 12 months. However, this virological response did not produce better immunological and clinical responses. The long-term impact of the ,32 deletion on survival in HIV-1-infected treated patients should be investigated in a meta-analysis. [source]

CD4 count and viral load time-courses in patients treated with highly active antiretroviral therapy and association with the CDC staging system

HIV MEDICINE, Issue 8 2006
J Collazos
Objectives The aim of the study was to analyse CD4 cell count and viral load dynamics in patients undergoing antiretroviral therapy and their association with the Centers for Disease Control and Prevention (CDC) classification system. Methods CD4 cell count and viral load were determined in 2982 patients who were classified according to clinical and immunological CDC stages. Measurements were carried out at baseline and at the 3rd, 6th and 12th months. Results Clear differences in the immunological and virological responses to therapy were observed depending on the CDC stage, with better results associated with less advanced stages. There was a marked parallelism in the CD4 cell count curves of the different CDC stages over the year of follow up, in both naïve and experienced patients, indicating that the increase in CD4 cell count at each time-point was similar for all clinical and immunological CDC stages. However, as the baseline values were closely associated with CDC stage, the CD4 cell counts finally reached were clearly dependent on CDC stage. The highest virological responses were observed during the initial 3 months, particularly in naïve patients, but whereas naïve patients showed additional increases up to the 6th month experienced patients reached a plateau at the 3rd month. The CD4 increases were also higher during the initial 3 months but persisted during the year of follow-up. Conclusion Both clinical and immunological CDC stages at baseline are highly predictive of the immunological and virological response to therapy, a finding that could have clinical implications. [source]

Determinants of response to first HAART regimen in antiretroviral-naïve patients with an estimated time since HIV seroconversion

HIV MEDICINE, Issue 1 2006
R Thiébaut
Objective To study the determinants of immunological and virological response to highly active antiretroviral therapy (HAART) in naïve patients, adjusting for time since HIV-1 seroconversion. Design Data from HIV-cohort studies where dates of seroconversion have been reliably estimated. Methods In previously untreated patients, short- and long-term marker responses from HAART initiation (three or more antiretroviral drugs) to the end of follow-up or any treatment modification were considered using mixed effects models accounting for undetectable HIV viral load and informative dropout. Results In total, 943 patients were treated with a first HAART regimen for a median of 29 months. In adjusted analyses, compared with a reference group of homosexual men without AIDS initiating treatment 4 years after seroconversion, injecting drug users (IDUs) were treated at similar CD4 and HIV RNA levels but had poorer short-term virological response (2.54 vs 2.13 log10 HIV-1 RNA copies/mL at 1.5 months, P=0.03) and poorer long-term immunological response (522 vs 631 cells/,L at 24 months, P<0.0001). Although individuals with AIDS at HAART initiation had lower CD4 counts (206 vs 382 cells/,L, P<0.0001), their immunological responses were similar to those of individuals without AIDS. Similarly, individuals further from seroconversion started HAART at lower CD4 counts (e.g. 311 vs 382 cells/,L at vs before 9 years from seroconversion, P<0.0001), but had similar CD4 responses. However, they experienced poorer long-term virological response (0.67 log10 copies/mL/year smaller decline, P<0.0001) compared to those treated before 9 years from seroconversion. Conclusion Taking into account the time elapsed since seroconversion, this study suggests that careful choices of initial treatment should be made and intensive follow-up carried out in high-risk subgroups such as IDUs who have poorer responses. [source]

Clinical features and predictors of survival of AIDS-related non-Hodgkin's lymphoma in a population-based case series in Sydney, Australia

HIV MEDICINE, Issue 5 2004
MC Robotin
Objectives To analyse clinical features and predictors of survival for AIDS-related non-Hodgkin's lymphoma (NHL) in the era of highly active antiretroviral therapy (HAART), compared to earlier in the HIV epidemic. Methods All AIDS-NHL cases diagnosed at three inner Sydney hospitals caring for people with AIDS during 1985,2001 were identified through medical record searches. Demographic, clinical, immunological and histopathological information was recorded. Year of NHL diagnosis was grouped into three periods, corresponding to whether monotherapy (1985,1991), dual therapy (1992,1995) or HAART (1996,2001) was the main treatment for HIV infection. Statistical comparisons were made between the pre-HAART and post-HAART eras. Results Three hundred cases of AIDS-NHL were identified. Divergent trends were identified for systemic and primary central nervous system (CNS) NHL. For systemic NHL, the CD4 count at NHL diagnosis increased markedly to 208 cells/,L in the post-HAART era (P=0.014) and there was a trend towards presentation as the first AIDS-defining illness (69%, P=0.053), and as earlier stage NHL disease (42%, P=0.048). Median survival time increased from 4.2 months in 1985,1991 to 19 months in the post-HAART era (P<0.001). In a multivariate model, predictors of poor survival from systemic NHL included: NHL diagnosis after another AIDS-defining illness (P<0.001), stage 4 NHL (P<0.001), presentation at extra lymphatic sites (P=0.001), and nonreceipt of chemotherapy (P=0.002). After adjusting for the factors, those diagnosed in the era of HAART had a significant 56% reduction in rate of death (P<0.001). In contrast, for CNS NHL, clinical features were little changed and survival did not improve in the era of HAART. Conclusions Systemic NHL is presenting earlier in the course of HIV disease, and at a less advanced NHL stage. There has been a marked improvement in survival in the era of HAART even after adjustment for other prognostic variables. In contrast, primary CNS NHL remains a disease which presents late in the course of HIV infection and is associated with a very poor prognosis. [source]

Association of IL4R gene polymorphisms with asthma in Chinese populations,,

HUMAN MUTATION, Issue 10 2007
Haibing Zhang
Abstract Cytokines, having central functions in immunological and inflammatory processes, are expected to play important roles in the pathogenesis of various diseases, such as asthma. Genetic polymorphisms of those cytokine and cytokine receptor genes are the focus of genetic association studies. In an effort to identify gene(s) whose variant(s) are associated with asthma, we screened all exons and their flanking regions, as well as the promoter region (1.5kb) of eight genes, including IL4, IL13, IL12B, IL5, IL3, IL9, CD14 and IL4R. We identified 42 single nucleotide polymorphisms, 15 of which were novel. Then, we examined the genetic effects of 30 single nucleotide polymorphisms in eight cytokine and cytokine receptor genes on asthma in a Chinese asthma cohort (n,=,537). Genetic association analysis of polymorphisms revealed that six polymorphisms (c.899-2C>A, c.1199A>C, c.1242G>T, c.1291T>C, c.1299T>C, c.1507T>C) in the IL4R gene, three of which resulted in an amino-acid change, showed significant association with the risk of asthma (P,=,0.00023). Further analysis indicates that these six polymorphisms segregated in strong linkage disequilibrium. The genetic association of IL4R with asthma might provide valuable insights into the pathogenesis of asthma. © 2007 Wiley-Liss, Inc. [source]

Inflammatory cytokine production by immunological and foreign body multinucleated giant cells

IMMUNOLOGY, Issue 3 2000
R. Hernandez-Pando
Summary Multinucleated giant cells (MGC) are a common feature of granulomas. The mechanism of their formation has been studied extensively, but their function has not been completely characterized. A new method for the in vivo production of MGC was developed involving subcutaneous injection of microscopic nitrocellulose particles with adsorbed mycobacterial antigens into the footpads of sensitized BALB/c mice (immune [I]-MGC), or by nitrocellulose administration to non-sensitized mice (foreign body [FB]-MGC). The development of granulomas with a highly enriched MGC population was observed 2 weeks after the nitrocellulose injection. MGC were larger with a greater number of nuclei in I-MGC than in FB-MGC. From days 7,28 after nitrocellulose administration, the production of interleukin-1, (IL-1,) and tumour necrosis factor-, (TNF-,) was demonstrated in both MGC types by in situ reverse transcription,polymerase chain reaction (RT,PCR) and immunohistochemistry. After 2 months, the MGC had ceased production of IL-1, and TNF-,, but the expression of transforming growth factor-, (TGF-,) was very high, occurring together with extensive fibrosis. These results suggest that MGC are an active source of inflammatory cytokines, which can contribute to the initiation, maintenance and down-regulation of granulomatous inflammation induced by immunological and inert substances. [source]

Inflammatory bowel disease: Epidemiology, pathogenesis, and therapeutic opportunities

INFLAMMATORY BOWEL DISEASES, Issue 5 2006
Stephen B Hanauer MD
Abstract Ulcerative colitis (UC) and Crohn's disease (CD), the primary constituents of inflammatory bowel disease (IBD), are precipitated by a complex interaction of environmental, genetic, and immunoregulatory factors. Higher rates of IBD are seen in northern, industrialized countries, with greater prevalence among Caucasians and Ashkenazic Jews. Racial gaps are closing, indicating that environmental factors may play a role. IBD is multigenic, with the most clearly established genetic link between certain NOD2 variants and CD. Regardless of the underlying genetic predisposition, a growing body of data implicates a dysfunctional mucosal immune response to commensal bacteria in the pathogenesis of IBD, especially CD. Possible triggers include a chronic inflammatory response precipitated by infection with a particular pathogen or virus or a defective mucosal barrier. The characteristic inflammatory response begins with an infiltration of neutrophils and macrophages, which then release chemokines and cytokines. These in turn exacerbate the dysfunctional immune response and activate either TH1 or TH2 cells in the gut mucosa, respectively associated with CD and, less conclusively, with UC. Elucidation of immunological and genetic factors indicate multiple points at which the inflammatory cascade may be interrupted, yielding the possibility of precise, targeted therapies for IBD. [source]

Nutritional and therapeutic value of fermented caprine milk

INTERNATIONAL JOURNAL OF DAIRY TECHNOLOGY, Issue 2 2010
ANAC, VEDRAN SLA
Caprine milk is a nutritional and therapeutic food. The unique and beneficial characteristics of caprine milk that are superior to bovine milk include: better digestibility; greater buffering capacity; fat globules that are smaller in diameter and better distributed in the milk emulsion; higher content of short-chain fatty acids in the milk fat; higher content of zinc, iron and magnesium; stronger lactoperoxidase (antimicrobial) system as well as better immunological and antibacterial characteristics. The larger amounts of some minerals, such as calcium, zinc and magnesium, in caprine milk may influence the growth of lactic acid bacteria since they are a normal part of some enzymatic complexes involved in lactose fermentation. The higher whey protein content could also be significant because Lactobacillus acidophilus and bifidobacteria grow better in the presence of higher levels of some amino acids (valine, glycine, hystidine). The use of caprine and ovine milk in cheesemaking is well known, but the production of fermented caprine milk via probiotics has not yet been developed, although many studies have highlighted the requirements for production of that kind of healthy food. During fermentation caprine milk loses its characteristic ,goaty' taste, which is unacceptable to many consumers. Moreover, the nutritive value of caprine milk increases during fermentation. The rise in the number of goat farms in Croatia has created the need to find other products that can be produced using caprine milk. According to the present situation in Croatia, there is no real possibility of producing fermented caprine milk for the global market, but many studies of fermented caprine milk have been performed. [source]

The effect of topical doxycycline usage on gingival crevicular fluid MMP-8 levels of chronic and aggressive periodontitis patients: a pilot study

INTERNATIONAL JOURNAL OF DENTAL HYGIENE, Issue 3 2006

Abstract:, The aim of this study was to evaluate the efficacy of topical subgingival application of doxycycline hyclate (DH) gel adjunctive to non-surgical periodontal therapy on gingival crevicular fluid (GCF) matrix metalloproteinase (MMP)-8 levels in chronic and aggressive periodontitis patients. Forty teeth of 10 chronic periodontitis patients and 32 teeth of eight aggressive periodontitis patients were screened for 6 months. Scaling and root planing (SRP) was applied to the control sites and DH gel adjunctive to SRP was applied to the test sites of each patient simultaneously. GCF MMP-8 levels were analysed at baseline, 7 days; and at 1, 3 and 6 months by Sandwich Elisa Method. At 1, 3 and 6 months, probing depth (P < 0.0051) and plaque scores and bleeding on probing values (P = 0.000) significantly decreased in each group when compared with the baseline, but there was no statistically significant difference between the test and control sites. GCF MMP-8 levels reduced presenting statistically significant differences on 7 days, 1, 3 and 6 months in four of the groups (P < 0.05); however, intergroup differences were not statistically significant. Developing functional and immunological-based chair-side MMP tests might serve as useful adjunctive diagnostic tools when monitoring the effects of DH gel application. [source]

Embryonic reversions and lineage infidelities in tumour cells: genome-based models and role of genetic instability

INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 2 2005
Leon P. Bignold
Summary Reversions to ,embryonic precursor'-type cells and infidelities of tumour cell lineage (including metaplasias) have been recognized as aspects of various tumour types since the 19th century. Since then, evidence of these phenomena has been obtained from numerous clinical, biochemical, immunological and molecular biological studies. In particular, microarray studies have suggested that ,aberrant' expressions of relevant genes are common. An unexplained aspect of the results of these studies is that, in many tumour types, the embryonic reversion or lineage infidelity only occurs in a proportion of cases. As a parallel development during the molecular biological investigation of tumours over the last several decades, genetic instability has been found much more marked, at least in some preparations of tumour cells, than that identified by means of previous karyotypic investigations of tumours. This study reviews examples of embryonic reversion and lineage infidelity phenomena, which have derived from the various lines of investigation of cancer over the last 150 or so years. Four categories of circumstances of the occurrence of embryonic reversions or lineage infidelities have been identified , (i) as part of the defining phenotype of the tumour, and hence being presumably integral to the tumour type, (ii) present ab initio in only some cases of the tumour type, and presumably being regularly associated with, but incidental to, the essential features of the tumour type, (iii) occurring later in the course of the disease and thus being possibly a manifestation of in vivo genetic instability and ,tumour progression' and (iv) arising probably by genetic instability, during the processes, especially cell culture, associated with ex vivo investigations. Genomic models are described which might account for the origin of these phenomena in each of these circumstances. [source]

Molecular biology and pathogenesis of the human T-cell leukaemia/lymphotropic virus Type-1 (HTLV-1)

INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 3 2001
Julie M. Johnson
Retroviruses are associated with a variety of diseases, including immunological and neurological disorders, and various forms of cancer. In humans, the Human T-cell Leukaemia/Lymphotropic virus type 1 (HTLV-1), which belongs to the Oncovirus family, is the aetiological agent of two diverse diseases: Adult T-cell leukaemia/lymphoma (ATLL) (Poiesz et al. 1980; Hinuma et al. 1981; Yoshida et al. 1982), as well as the neurological disorder tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM) (Gessain et al. 1985; Rodgers-Johnson et al. 1985; Osame et al. 1986). HTLV-1 is the only human retrovirus known to be the aetiological agent of cancer. A genetically related virus, HTLV-2, has been identified and isolated (Kalyanaraman et al. 1982). However, there has been no demonstration of a definitive aetiological role for HTLV-2 in human disease to date. Simian T-cell lymphotropic viruses types 1 and 2 (STLV-1 and -2) and bovine leukaemia virus (BLV) have also been classified in same group, Oncoviridae, based upon their similarities in genetic sequence and structure to HTLV-1 and -2 (Burny et al. 1988; Dekaban et al. 1995; Slattery et al. 1999). This article will focus on HTLV-1, reviewing its discovery, molecular biology, and its role in disease pathogenesis. [source]

Combined pulmonary toxicity of cadmium chloride and sodium diethyldithiocarbamate

JOURNAL OF APPLIED TOXICOLOGY, Issue 2 2001
Erzsébet Tátrai
Abstract The pulmonary toxicity of sodium diethyldithiocarbamate and cadmium chloride, each separately and in combination, was compared in Sprague-Dawley rats after single intratracheal instillation in sequential experiments by chemical, immunological and morphological methods. With combined exposure, the cadmium content of the lungs increased permanently relative to that of the lungs of just cadmium-treated animals. Immunoglobulin levels of the whole blood did not change, whereas in bronchoalveolar lavage the IgA and IgG levels increased significantly. Morphological changes were characteristic of the effects of cadmium but were more extensive and more serious than in the case of cadmium administration alone: by the end of the first month, interstitial fibrosis, emphysema and injury of membranes of type I pneumocytes developed and hypertrophy and loss of microvilli in type II pneumocytes were detectable. These results showed that although dithiocarbamates as chelating agents are suitable for the removal of cadmium from organisms, they alter the redistribution of cadmium within the organism, thereby increasing the cadmium content in the lungs, and structural changes are more serious than observed upon cadmium exposure alone. Copyright © 2001 John Wiley & Sons, Ltd. [source]

Diphenyl diselenide protects against hematological and immunological alterations induced by mercury in mice

JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 5 2008
Ricardo Brandão
Abstract Mercury is a heavy metal that can cause a variety of toxic effects on the organism, such as hematological and immunological alterations. In the present investigation, deleterious effects of mercury-intoxication in mice and a possible protective effect of diphenyl diselenide (PhSe)2 were studied. Male adult Swiss albino mice received daily a pretreatment with (PhSe)2 (15.6 mg/kg, orally) for 1 week. After this week, mice received daily mercuric chloride (1 mg/kg, subcutaneously) for 2 weeks. A number of hematological (erythrocytes, leukocytes, platelets, hemoglobin, hematocrit, reticulocytes, and leukocytes differential) and immunological (immunoglobulin G and M plasma concentration) parameters were evaluated. Another biomarker of tissue damage, lactate dehydrogenase (LDH), was also determined. The results demonstrated that mercury exposure caused a reduction in the erythrocyte, hematocrit, hemoglobin, leukocyte, and platelet counts and an increase in the reticulocyte percentages. (PhSe)2 was effective in protecting against the reduction in hematocrit, hemoglobin, and leukocyte levels. (PhSe)2 ameliorated reticulocyte percentages increased by mercury. However, (PhSe)2 was partially effective in preventing against the decrease in erythrocyte and platelet counts. Immunoglobulin G and M concentrations and LDH activity were increased by mercury exposure, and (PhSe)2 was effective in protecting against these effects. In conclusion, (PhSe)2 was effective in protecting against hematological and immunological alterations induced by mercury in mice. © 2008 Wiley Periodicals, Inc. J Biochem Mol Toxicol 22:311,319, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20242 [source]

Molecular, immunological and clinical properties of mutated hepatitis B viruses

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 1 2002
C. Kreutz
Abstract Hepatitis B virus (HBV) is at the origin of severe liver diseases like chronic active hepatitis, liver cirrhosis and hepatocellular carcinoma. There are some groups of patients with high risk of generation of HBV mutants: infected infants, immunosupressed individuals (including hemodialysis patients), patients treated with interferon and lamivudine for chronic HBV infection. These groups are the target for molecular investigations reviewed in this paper. The emergence of lamivudine- or other antiviral-resistant variants, rises concern regarding long term use of these drugs. Infection or immunization with one HBV subtype confers immunity to all subtypes. However, reinfection or reactivation of latent HBV infection with HBV mutants have been reported in patients undergoing transplant and those infected with HIV. Mutations of the viral genome which are not replicative incompetent can be selected in further course of infection or under prolonged antiviral treatment and might maintain the liver disease. Four open reading frames (ORF) which are called S-gene, C-gene, X-gene and P-gene were identified within the HBV genome. Mutations may affect each of the ORFs. Mutated S-genes were described to be responsible for HBV-infections in successfully vaccinated persons, mutated C-genes were found to provoke severe chronic liver diseases, mutated X-genes could cause serious medical problemes in blood donors by escaping the conventional test systems and mutated P-genes were considered to be the reason for chemotherapeutic drug resistance. This paper reviews molecular, immunological and clinical aspects of the HBV mutants. [source]