Primary ovarian leiomyoma is a rare benign tumour of the ovary, which is seen in women who are aged between 20 years to 65 years. Ovarian leiomyomas can be confused with other spindle cell tumours which display gross anatomical and histological similarities. A case of a primary leiomyoma of the ovary in a pre-menopausal female is being presented here, due to its huge size and unusual presentation.
Ovarian leiomyoma; Primary tumour; Benign; Huge; Secondary changes
Trigeminal neuralgia (TN) is by no means an uncommon entity presenting as typical or atypical pain syndrome with a standard treatment protocol consisting of medical and surgical therapies. The diagnosis of TN is mainly dependent on the characteristics of symptoms conveyed by the patient and the clinical presentation. Careful history taking, proper interpretation of the signs and symptoms and cranial nerve assessment are necessary for proper diagnosis. Here, we report a case of TN, treated for dental problems and then for neuralgia with only short-term relief. Subsequently, the patient underwent neuroimaging and was found to be having an uncommon space-occupying lesion in the posterior cranial fossa.
Posterior cranial fossa tumor; trigeminal neuralgia; cerebello-pontine angle tumors
A potent immunomodulatory role of Vitamin D in both innate and adaptive immunity has recently been appreciated. In allergic asthma, activation of NF-κB induces transcription of various cytokines and chemokines involved in allergic airway inflammation. The nuclear import of activated NF-κB p50/RelA subunit is dependent on importin α3 (KPNA4) and importin α4 (KPNA3). In this study, we examined the role of importin α3 in immunomodulatory effect of calcitriol in human bronchial smooth muscle cells (HBSMCs).
Cultured HBSMCs were stimulated with calcitriol in the presence and absence of cytokines, TNF-α, IL-1β, and IL-10. The mRNA transcripts of importin α3 and α4 were analyzed using qPCR while protein expression of importin α3, α4 and nuclear RelA was analyzed by immunoblotting.
Calcitriol significantly decreased mRNA and protein expression of importin α3 as well as nuclear protein expression of NF-κB p65 (RelA). The decreased activation of RelA by calcitriol was confirmed by decreased release of RelA-inducible molecules, including IL-5, IL-6 and IL-8, by HBSMCs upon calcitriol treatment. Calcitriol attenuated the effect of TNF-α and IL-1β to upregulate mRNA and protein expression of importin α3. IL-10 significantly decreased the TNF-α induced expression of importin α3 and this effect was further potentiated by calcitriol.
These data suggest that under inflammatory conditions, calcitriol decreases the expression of importin α3 resulting in decreased nuclear import of activated RelA. This could be a novel mechanism by which calcitriol could exert its immunomodulatory effects to reduce allergic airway inflammation and thus may alleviate the symptoms in allergic asthma.
Active vitamin D; Allergic airway inflammation; Asthma; Bronchial smooth muscle cells; Calcitriol; Importinα3 (KPNA4); Importinα4 (KPNA3); NF-κB; Vitamin D receptor (VDR)
Aim: This study has compared the Shear Bond Strengths (SBSs) of ceramic brackets and metal brackets.
Materials and Method: Forty freshly extracted, human maxillary first premolars were selected for bonding. They were equally bonded with ceramic brackets (Transcend series 6000) and metal brackets (Mini Dynalock Straight wire brackets). A no – mix orthodontic adhesive system was used. Their shear bond strengths were measured by using the Instron universal machine.
Results: The mean bond strength of the ceramic brackets was 20.68 ± 3.89 Mpa and that of the metal brackets was 12.15 ± 1.32 MPa.
Conclusion: The shear bond strength of the ceramic brackets was found to be superior than that of the metal brackets.
Bracket; Ceramic; Metal; Shear bond
Asthma is one of the most common chronic inflammatory diseases of the airways. Calcitriol exerts its action through Vitamin D receptor (VDR), which is a high affinity nuclear receptor. VDR is a transcription factor that alters the transcription of target genes which are involved in a wide spectrum of biological responses. Lower serum vitamin D levels are associated with airway hyperresponsiveness and increased asthma severity. Prohibitin is a ubiquitously expressed protein localized to the cell and mitochondrial membranes and the nucleus.
Methods and results
HBSMCs were cultured and treated with calcitriol and/or TNF-α. The mRNA and protein expression of prohibitin and VDR were analyzed using qPCR and immunoblotting, respectively. In the in vivo studies, female BALB/c mice were fed with special vitamin D-deficient or 2,000 IU/kg of vitamin D-supplemented diet for 13 weeks. Mouse model of allergic airway inflammation was developed by OVA-sensitization and challenge. The expression pattern of TNF-α, prohibitin and VDR in the lung of OVA-sensitized mice was analyzed using immunofluorescence. Calcitriol significantly increased and TNF-α decreased the protein and mRNA expression of prohibitin and VDR in HBSMCs. There was significantly increased expression of TNF-α and decreased expression of VDR and prohibitin in the lung of vitamin D-deficient mouse model of allergic airway inflammation.
These results suggest that under inflammatory conditions there is decreased expression of VDR resulting in decreased expression of prohibitin, which is a vitamin D target gene. Vitamin D deficiency causes increase in the expression of TNF-α, thereby increasing inflammation and decreases the expression of VDR and prohibitin. Supplementation with vitamin D reduces the levels of TNF-α, thereby increasing the expression of VDR and prohibitin that could be responsible for reducing allergic airway inflammation.
Allergic airway inflammation; Asthma; Human Bronchial Smooth Cells; Inflammation; Prohibitin; TNF-α; Vitamin D receptor; Vitamin D
Vitamin D is a sectosteroid that functions through Vitamin D receptor (VDR), a transcription factor, which controls the transcription of many targets genes. Vitamin D deficiency has been linked with cardiovascular diseases, including heart failure and coronary artery disease. Suppressor of cytokine signaling (SOCS)3 regulates different biological processes such as inflammation and cellular differentiation and is an endogenous negative regulator of cardiac hypertrophy.
The purpose of this study was to test the hypothesis that vitamin D deficiency causes cardiomyocyte hypertrophy and increased proinflammatory profile in epicardial adipose tissue(EAT), and this correlates with decreased expression of SOCS3 in cardiomyocytes and EAT.
Eight female Yucatan miniswine were fed vitamin D-sufficient (900 IU/d) or vitamin D-deficient hypercholesterolemic diet. Lipid profile, metabolic panel, and serum 25(OH)D levels were regularly measured. After 12 months animals were euthanized and histological, immunohistochemical and qPCR studies were performed on myocardium and epicardial fat.
Histological studies showed cardiac hypertrophy, as judged by cardiac myocyte cross sectional area, in vitamin D-deficient group. Immunohistochemical and qPCR analyses showed significantly decreased mRNA and protein expression of VDR and SOCS3 in cardiomyocytes of vitamin D-deficient animals. EAT from vitamin D-deficient group had significantly higher expression of TNF-α, IL-6, MCP-1, and decreased adiponectin in association with increased inflammatory cellular infiltrate. Interestingly, EAT from vitamin D-deficient group had significantly decreased expression of SOCS3.
These data suggest that vitamin D deficiency induces hypertrophy in cardiomyocytes which is associated with decreased expression of VDR and SOCS3. Vitamin D deficiency is also associated with increased inflammatory markers in EAT. Activity of VDR in the body is controlled through regulation of vitamin D metabolites. Therefore, restoration of VDR function by supplementation of VDR ligands in vitamin D- deficient population might be helpful in reducing inflammation and cardiovascular risk.
Cardiac Hypertrophy; Coronary Artery Disease; Epicardial Fat; Inflammation; Vitamin D
Background This study explored the relationship between the knowledge of community health workers (CHWs)—anganwadi workers (AWWs) and auxiliary nurse midwives (ANMs)—and their antenatal home visit coverage and effectiveness of the visits, in terms of essential newborn health care practices at the household level in rural India.
Methods We used data from 302 AWWs and 86 ANMs and data from recently delivered women (RDW) (n = 13 023) who were residents of the CHW catchment areas and gave birth to a singleton live baby during 2004–05. Using principal component analysis, knowledge scores for preventive care and danger signs were computed separately for AWWs and ANMs and merged with RDW data. A multivariate logistic regression model was used to estimate the adjusted effect of knowledge level. A generalized estimating equation (GEE) was used to account for clustering.
Results Coverage of antenatal home visits and newborn care practices were positively correlated with the knowledge level of AWWs and ANMs. Initiation of breastfeeding in the first hour of life (odds ratio 1.97; 95% confidence interval (CI): 1.55–2.49 for AWW, and odds ratio 1.62; 95% CI: 1.25–2.09 for ANM), clean cord care (odds ratio 2.03; 95% CI: 1.64–2.52 for AWW, and odds ratio 1.43; 95% CI: 1.17–1.75 for ANM) and thermal care (odds ratio 2.16; 95% CI: 1.64–2.85 for AWW and odds ratio 1.88; 95% CI: 1.43–2.48 for ANM) were significantly higher among women visited by AWWs or ANMs who had better knowledge compared with those with poor knowledge.
Conclusion CHWs’ knowledge is one of the crucial aspects of health systems to improve the coverage of community-based newborn health care programmes as well as adherence to essential newborn care practices at the household level.
Knowledge level; community health workers; essential newborn health care practices; principal component analysis; logistic regression; generalized estimating equation
The immune system has evolved to mount immune responses against foreign pathogens and to remain silent against self-antigens. A balance between immunity and tolerance is required as any disturbance may result in chronic inflammation or autoimmunity. Dendritic cells (DCs) actively participate in maintaining this balance. Under steady-state conditions, DCs remain in an immature state and do not mount an immune response against circulating self-antigens in the periphery, which maintains a state of tolerance. By contrast, foreign antigens result in DC maturation and DC-induced T-cell activation. Inappropriate maturation of DCs due to infections or tissue injury may cause alterations in the balance between the tolerogenic and immunogenic functions of DCs and instigate the development of autoimmune diseases. This article provides an overview of the effects of advancing age on DC functions and their implications in autoimmunity.
aging; autoimmunity; dendritic cells; self-tolerance
Post-operative course after complex pediatric cardiac surgery is unpredictable. Although, change in arterial lactate levels has been used as a surrogate marker for many years, scientific evidence correlating the early perioperative lactate levels with outcome is still lacking.
To evaluate the trends in lactate levels from intraoperative period to an extended post-operative period in pediatric intensive care unit (PICU) and to assess its usefulness as a prognostic marker.
Prospective observational study.
Tertiary pediatric cardiac surgical unit.
Thirty-five non-consecutive children aged 1-140 months who underwent surgery for congenital heart diseases (CHD) on cardiopulmonary bypass (CPB).
Materials and Methods:
Arterial blood lactate levels were obtained at the following time points: After induction of anesthesia, 15 and 45 min after institution of CPB, at the start of rewarming, after sternotomy closure, then at 1, 6, 24, and 48 h in PICU. Other hemodynamic and clinical variables, CPB variables, blood gas values, and laboratory variables were also recorded.
Four patients died out of 35 patients (11.4%). Non-survivors showed significant persistent elevation in lactates (>4.0 mmol/l). Peak lactates correlate significantly with longer aortic cross clamp time, CPB duration, ventilation hours and PICU stay.
Early point of care lactate can be a useful prognostic marker in post-cardiac surgery patients in adjunct with other parameters measured in PICU. This reiterates the importance of measuring lactates and timely recognition of at-risk patients, which on early intervention can help in reducing post-operative morbidity and mortality.
Children; pediatric cardiac surgery; plasma lactate
Advancing age leads to significant decline in immune functions. IL-21 is produced primarily by T follicular helper (Tfh) cells and is required for effective immune cell functions. Here we compared the induction of IL-21 in aged and young subjects. Our investigation demonstrates that CD4+T cells from healthy elderly individuals (age ≥ 65) secreted significantly higher levels of IL-21 on priming with aged and young dendritic cells (DC). Though the aged and young DCs secreted comparable levels of IL-12 on stimulation with anti-CD40 antibody and LPS, culture of DCs with aged CD4+ T cells resulted in increased production of IL-21 as compared to that with young CD4+ T cells. Further examination revealed that the response of aged naïve CD4+ T cells to IL-12 was altered, resulting in increased differentiation of aged Th cells towards Tfh cells. Investigation into the signaling mechanism suggested that phosphorylation of STAT-4 in response to IL-12 was sustained for a longer duration in aged CD4+ T cells as compared to CD4+ T cells from young subjects. Additional analysis demonstrated that increased IL-21 secretion correlated with chronic CMV infection in aged subjects. These findings indicate that chronic CMV infection alters the response of aged CD4+ T cells to IL-12 resulting in an increased secretion of IL-21 and that aging affects Tfh cell responses in humans which may contribute to age-associated inflammation and immune dysfunctions.
Aging; CD4+ T cells; IL-21; T follicular helper cells; STAT-4; Cytomegalovirus
Inflammatory cytokines, such as TNF-α, play a key role in the pathogenesis of occlusive vascular diseases. Activation of vitamin D receptors (VDR) elicits both growth-inhibitory and anti-inflammatory effects. Here, we investigated the expression of TNF-α and VDR in post-angioplasty coronary artery neointimal lesions of hypercholesterolemic swine and examined the effect of vitamin D deficiency on the development of coronary restenosis. We also examined the effect of calcitriol on cell proliferation and effect of TNF-α on VDR activity and expression in porcine coronary artery smooth muscle cells (PCASMCs) in-vitro.
Expression of VDR and TNF-α and the effect of vitamin D deficiency in post-angioplasty coronary arteries were analyzed by immunohistochemistry and histomorphometry. Cell proliferation was examined by thymidine and BrdU incorporation assays in cultured PCASMCs. Effect of TNF-α-stimulation on the activity and expression of VDR was analyzed by luciferase assay, immunoblotting and immunocytochemistry. In-vivo, morphometric analysis of the tissues revealed typical lesions with significant neointimal proliferation. Histological evaluation showed expression of smooth muscle α-actin and significantly increased expression of TNF-α in neointimal lesions. Interestingly, there was significantly decreased expression of VDR in PCASMCs of neointimal region compared to normal media. Indeed, post-balloon angioplasty restenosis was significantly higher in vitamin D-deficient hypercholesterolemic swine compared to vitamin D-sufficient group. In-vitro, calcitriol inhibited both serum- and PDGF-BB-induced proliferation in PCASMCs and TNF-α-stimulation significantly decreased the expression and activity of VDR in PCASMCs.
These data suggest that significant downregulation of VDR in proliferating smooth muscle cells in neointimal lesions could be due to atherogenic cytokines, including TNF-α. Vitamin D deficiency potentiates the development of coronary restenosis. Calcitriol has anti-proliferative properties in PCASMCs and these actions are mediated through VDR. This could be a potential mechanism for uncontrolled growth of neointimal cells in injured arteries leading to restenosis.
Perinatal asphyxia leading to hypoxic-ischemic encephalopathy (HIE) is a common problem causing multi organ dysfunction including myocardial involvement which can affect the outcome.
To evaluate the myocardial dysfunction in neonates having HIE by electrocardiographic(ECG) and cardiac enzymes (CK Total, CK-MB and Troponin I) and find out the relationship with HIE and outcome.
This was a hospital based prospective study. Sixty term neonates who had suffered perinatal asphyxia and developed HIE were enrolled. Myocardial involvement was assessed by clinical, ECG, and CK Total, CK-MB and Troponin I measurements.
Of 60 cases, 13(21.7%) were in mild, 27(45%) in moderate and 20(33.3%) belonged to severe,HIE. ECG was abnormal in 46 (76.7%); of these 19 (41.3%) had grade I, 13 (28.2%) grades II and III each and 1 (2.1%) with grade IV changes. Serum levels of CK Total, CK- MB and Troponin I were raised in 54 (90%), 52 (86.6%) and 48 (80%) neonates, respectively. ECG changes and enzymatic levels showed increasing abnormalities with severity of HIE, and the differences among different grades were significant (p = 0.002, 0.02, <0.001 and 0.004, respectively). Nineteen (32%) cases died during hospital stay. The non- survivors had high proportion of abnormal ECG (p = 0.024), raised levels of CK-MB (p = 0.018) and Troponin I (p = 0.008) in comparison to survivors.
Abnormal ECG and cardiac enzymes levels are found in HIE and can lead to poor outcome due to myocardial damage Early detection can help in better management and survival of these neonates.
Perinatal asphyxia; HIE; Myocardial dysfunction
Amiodarone, class III anti-arrhythmic was originally introduced to treat angina pectoris, was later approved by FDA in 1985 for the treatment of ventricular arrhythmias. Despite its anti-arrhythmic properties, amiodarone is associated with side effects such as thyroid dysfunction, corneal deposits, bluish skin discoloration, neuropathy and pulmonary toxicity. Amiodarone induced pulmonary toxicity (AIPT) is one of the most serious side effect thus limiting its use.
We encountered a 66 year old male with early onset AIPT who presented with dyspnea and chest imaging revealed extensive ground-glass opacities throughout lung parenchyma with rapid resolution of these opacities in a week following treatment with corticosteroids.
There have been few case reports of AIPT with complete resolution of ground glass opacities on treatment with corticosteroids, but none demonstrated a rapid response to corticosteroids. Heath care providers should withdraw amiodarone at the earliest suspicion (as illustrated in our case); any delay can potentially be fatal. This case highlights the fact that AIPT is a reversible phenomenon, provided its early recognition and treatment before fibrosis sets in This case also highlights the need to include AIPT in the differential diagnosis in any patient on amiodarone who presents with shortness of breath.
amiodarone; interstitial lung disease; lung toxicity
This paper reviews the various aspects of tissue regeneration during the process of tissue expansion. “Creep” and mechanical and biological “stretch” are responsible for expansion. During expansion, the epidermis thickens, the dermis thins out, vascularity improves, significant angiogenesis occurs, hair telogen phase becomes shorter and the peripheral nerves, vessels and muscle fibres lengthen. Expansion is associated with molecular changes in the tissue. Almost all these biological changes are reversible after the removal of the expander.This study is also aimed at reviewing the difficulty in deciding the volume and dimension of the expander for a defect. Basic mathematical formulae and the computer programmes for calculating the dimension of tissue expanders, although available in the literature, are not popular. A user-friendly computer programme based on the easily available Microsoft Excel spread sheet has been introduced. When we feed the area of defect and base dimension of the donor area or tissue expander, this programme calculates the volume and height of the expander. The shape of the expander is decided clinically based on the availability of the donor area and the designing of the future tissue movement. Today, tissue expansion is better understood biologically and mechanically. Clinical judgement remains indispensable in choosing the size and shape of the tissue expander.
Mathematics of tissue expansion; tissue expander; tissue expansion; tissue regeneration
We previously reported that Fms-like tyrosine kinase 3 ligand (Flt3-L) reversed airway hyperresponsiveness (AHR) and airway inflammation, and increased the number of regulatory CD11chighCD8αhighCD11blow dendritic cells and CD4+CD25+ICOS+Foxp3+IL-10+ T-regulatory cells in the lung of allergen-sensitized and -challenged mice. In this study, we evaluated the effect of Flt3-L on Th17 cells and expression of suppressors of cytokine signaling (SOCS) proteins in the lungs of house dust mite (HDM)–sensitized and –challenged mice. BALB/c mice were sensitized and challenged with HDM, and AHR to methacholine was established. Mice were treated with Flt3-L (5 μg, intraperitoneal) daily for 10 days. Levels of IL-4, -5, -6, -8, and -13, and transforming growth factor (TGF)–β in the bronchoalveolar lavage fluid (BALF) were examined by ELISA. Flt3-L treatment reversed existing AHR to methacholine and substantially decreased eosinophils, neutrophils, IL-5, -6, -8, and IL-13, and TGF-β levels in the BALF. HDM-sensitized and -challenged mice showed a significant increase in lung CD4+IL-17+IL-23R+CD25− T cells with high expression of retinoic acid–related orphan receptor (ROR)–γt transcripts. However, administration of Flt3-L substantially decreased the number of lung CD4+IL-17+IL-23R+CD25− T cells, with significantly decreased expression of ROR-γt mRNA in these cells. HDM sensitization caused a significant increase in the expression of SOCS-1, -3, and -5 in the lung. Flt3-L treatment abolished the increase in SOCS-1 and SOCS-3 proteins, whereas SOCS-5 expression was significantly reduced. These data suggest that the therapeutic effect of Flt3-L in reversing the hallmarks of allergic asthma in a mouse model is mediated by decreasing IL-6 and TGF-β levels in the BALF, which, in turn, decrease CD4+IL-17+IL-23R+ROR-γt+CD25− T cells and the expression of SOCS-1 and SOCS-3 in the lung of HDM-sensitized and -challenged mice.
airway hyperresponsiveness; house dust mite; retinoic acid–related orphan receptor–γt; suppressors of cytokine signaling; T helper cell type 17
Warkany syndrome 2 or Trisomy 8 mosaicism (T8M) is a well-described, but very rare, chromosomal abnormality. The phenotype is extremely variable ranging from normal individual to severe malformation syndrome and because of this variability, this condition often goes undiagnosed. We report trisomy 8 mosaicism (T8M) in a 3-year-old boy evaluated for facial dysmorphism and delayed development.
To assess the surgical outcome of myasthenia gravis (MG) following thymectomy and to determine the outcome predictors to such therapeutic approach.
Materials and Methods:
This study is a retrospective review of 80 consecutive thymectomies performed for MG over a 16-year period.
There were 41 females and 39 males (mean age, 34.32 years) with mean disease duration of 17.45 months prior to surgery. Stagewise distribution of the patients revealed 2.5% in stage I, 48.7% in stage IIA, 33.8% in stage IIB, 8.7% in stage III, and 6.3% in stage IV. The surgical approach was either trans-sternal (n=67) or video-assisted thoracoscopic route (n=13). Follow-up was obtained in 91.2% (n=73) of patients with mean duration of 67.7 months. At their last follow-up, 26.0% were in complete remission, 35.6% were asymptomatic on decreased medications, and 17.8% had clinical improvement on decreased medications. Overall, 79.4% of patients benefited from surgery, 8.2% had unchanged disease status, and 12.3% worsened clinically. Factors influencing favorable outcome include sex, disease stage, gland weight, and preoperative medication with anti-cholinesterase (P<0.05). There was one death in the perioperative period due to septicemia. Two patients died at fourth and seventh month following thymectomy.
Thymectomy for MG is safe and effective. Certain influencing factors may shape treatment decisions and target higher risk patients.
Myasthenia gravis; thymectomy; video-assisted thymectomy
Non-Hodgkin's lymphomas are a group of neoplasms that originate from the cells of the lymphoreticular system. Forty percent of non-Hodgkin's lymphomas arise from extra nodal sites. Non-Hodgkin's lymphomas detected primarily in the bone are quite rare, but among jaw lesions, they are more frequently present in the maxilla than in the mandible. There are no classical characteristic clinical features of lymphomas involving the jaw bones. Swelling, ulcer or discomfort may be present in the region of the lymphoma, or it may mimic a periapical pathology or a benign condition. Extranodal non-Hodgkins lymphoma of the maxilla could present as one of the early manifestation of detrimental diseases. Clinically these types of lymphoma can mimic an inflammatory endo-periodontal lesion with symptoms of pain and local discomfort. The greater the delay in diagnosis subsequently worsens the prognosis. A case of maxillary non-Hodgkin's lymphoma with an unusual presentation is discussed.
Non-Hodgkin's lymphoma; maxilla; rare entity
Dentigerous cysts are always associated with an embedded or unerupted tooth; involvement of more than one permanent tooth in a single cyst follicle is exceedingly rare and only a few such cases can be found in the literature. The cysts reported in the literature involving multiple teeth typically consist of mesiodens or odontomas. Here we report a rare case of dentigerous cyst associated with two permanent teeth causing displacement of maxillary canine into the osteo meatal complex and maxillary premolar to lateral nasal wall. The possible etiopathogenesis of such cases is also discussed here.
Dentigerous cyst; multiple teeth; tooth displacement
The parasitic microhabitat distribution of the monogenoideans Thaparocleidus wallagonoius Jain, 1952, Mizelleus indicus Jain, 1957and T. gomtius Jain, 1957 parasitizing the gills of a fresh-water demersal Wallago attu and their seasonal variations were investigated in the present study. The microhabitat preferences of these species were observed. The gill segments and gill areas were the most important factors segregating the monogenoidean parasites on gills, not their abundance. Low niche overlap was found within each of the four gill arches and parasites were segregated in the same microhabitats within each gill arch. The distribution of parasites was independent of the left or right side of gill. The distribution plots in our study indicated that the anterior segment of first and fourth gill arches were more preferred site of infection. Seasonal variation of parasites, recorded during 2006 & 2007, in male and female hosts was also investigated. Due to ectoparasitic nature and high host specificity exhibited by the species of monogenoidea, studies on their seasonal dynamics are very significant as they could contribute significantly to the understanding of their biological adaptations to their environment.
Gill arch; Microhabitat; Monogenoideans; Seasonal variation
Dendritic cells capture antigens through PRRs and modulate adaptive immune responses. The type of adaptive immune T cell response generated is dependent upon the type of PRR activated by the microbes. Dectin-1 is a C-type lectin receptor present on dendritic cells.
Here we show that selective dectin-1 agonist Curdlan can activate human DCs and induce the secretion of large amounts of IL-23, IL-1β, IL-6 and low levels of IL-12p70 as determined by ELISA. The Curdlan-stimulated DCs are efficient at priming naïve CD4 cells to differentiate into Th17 and Th1 cells. Furthermore, these CD4 T cells induce differentiation of B cells to secrete IgG and IgA. In addition, Curdlan-stimulated DCs promote the expansion and differentiation of Granzyme and perforin expressing cytotoxic T lymphocyte that display high cytolytic activity against target tumor cells in vitro.
These data demonstrate that DCs stimulated through Dectin-1 can generate efficient Th, CTL and B cell responses and can therefore be used as effective mucosal and systemic adjuvants in humans.
Increased susceptibility to infections, particularly respiratory viral infections, is a hallmark of advancing age. The underlying mechanisms are not well understood, and there is a scarcity of information regarding the contribution of the innate immune system, which is the first line of defense against infections. In the present study, we have investigated the effect of advancing age on plasmacytoid dendritic cell (PDC) function because they are critical in generating a robust antiviral response via the secretion of interferons (IFN). Our results indicate that PDCs from the aged are impaired in their capacity to secrete IFN-I in response to influenza virus and CPG stimulation. Additionally, we observed a severe reduction in the production of IFN-III, which plays an important role in defense against viral infections at respiratory mucosal surfaces. This reduction in IFN-I and IFN-III were a result of age-associated impaired phosphorylation of transcription factor, IRF-7. Furthermore, aged PDCs were observed to be impaired in their capacity to induce perforin and granzyme in CD8 T cells. Comparison of the antigen-presenting capacity of aged PDC with young PDC revealed that PDCs from aged subjects display reduced capacity to induce proliferation and IFN-gamma secretion in CD4 and CD8 T cells as compared with PDCs from young subjects. In summary, our study demonstrates that advancing age has a profound effect on PDC function at multiple levels and may therefore, be responsible for the increased susceptibility to infections in the elderly.
Plasmacytoid dendritic cells; Aging; Influenza; Type I interferons; Type III interferons; CD8 cytotoxicity; T cell proliferation
Synchronous bilateral germ cell tumo (BGCT) of the testis is rare and its association with bilateral cryptorchidism is even rarer. We report one case of BGCT of testis with bilateral cryptorchidism who presented as blunt injury abdomen in emergencyand was not diagnosed preoperatively. Postoperatively after an appropriate diagnosis, he was managed with chemotherapy. In this report, we have reviewed the larger series of BGCT for the presentation and management of synchronous BGCT to derive some conclusions.
Bilateral germ cell tumor; synchronous; testicular tumor