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1.
Reprod Health ; 20(1): 18, 2023 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-36670438

RESUMEN

BACKGROUND: The World Health Organization (WHO) Labour Care Guide (LCG) is a paper-based labour monitoring tool designed to facilitate the implementation of WHO's latest guidelines for effective, respectful care during labour and childbirth. Implementing the LCG into routine intrapartum care requires a strategy that improves healthcare provider practices during labour and childbirth. Such a strategy might optimize the use of Caesarean section (CS), along with potential benefits on the use of other obstetric interventions, maternal and perinatal health outcomes, and women's experience of care. However, the effects of a strategy to implement the LCG have not been evaluated in a randomised trial. This study aims to: (1) develop and optimise a strategy for implementing the LCG (formative phase); and (2) To evaluate the implementation of the LCG strategy compared with usual care (trial phase). METHODS: In the formative phase, we will co-design the LCG strategy with key stakeholders informed by facility assessments and provider surveys, which will be field tested in one hospital. The LCG strategy includes a LCG training program, ongoing supportive supervision from senior clinical staff, and audit and feedback using the Robson Classification. We will then conduct a stepped-wedge, cluster-randomized pilot trial in four public hospitals in India, to evaluate the effect of the LCG strategy intervention compared to usual care (simplified WHO partograph). The primary outcome is the CS rate in nulliparous women with singleton, term, cephalic pregnancies in spontaneous labour (Robson Group 1). Secondary outcomes include clinical and process of care outcomes, as well as women's experience of care outcomes. We will also conduct a process evaluation during the trial, using standardized facility assessments, in-depth interviews and surveys with providers, audits of completed LCGs, labour ward observations and document reviews. An economic evaluation will consider implementation costs and cost-effectiveness. DISCUSSION: Findings of this trial will guide clinicians, administrators and policymakers on how to effectively implement the LCG, and what (if any) effects the LCG strategy has on process of care, health and experience outcomes. The trial findings will inform the rollout of LCG internationally. TRIAL REGISTRATION: CTRI/2021/01/030695 (Protocol version 1.4, 25 April 2022).


The new WHO Labour Care Guide (LCG) is an innovative partograph that emphasises women-centred, evidence-based care during labour and childbirth. Together with clinicians working at four hospitals in India, we will develop and test a strategy to implement the LCG into routine care in labour wards of these hospitals. We will use a randomised trial design where this LCG strategy is introduced sequentially in each of the four hospitals, in a random order. We will collect data on all women giving birth and their newborns during this period and analyse whether the LCG strategy has any effects on the use of Caesarean section, women's and newborn's health outcomes, and women's experiences during labour and childbirth. While the trial is being conducted, we will also collect qualitative and quantitative data from doctors, nurses and midwives working in these hospitals, to understand their perspectives and experiences of using the LCG in their day-to-day work. In addition, we will collect economic data to understand how much the LCG strategy costs, and how much money it might save if it is effective. Through this study, our international collaboration will generate critical evidence and innovative tools to support implementation of the LCG in other countries.


Asunto(s)
Cesárea , Parto , Femenino , Humanos , Embarazo , Hospitales , Proyectos Piloto , Ensayos Clínicos Controlados Aleatorios como Asunto , Organización Mundial de la Salud , Ensayos Clínicos Pragmáticos como Asunto
2.
J Obstet Gynaecol India ; 72(Suppl 1): 255-261, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35928072

RESUMEN

Objective: 1. To determine the prevalence of pre malignant cervical lesions in HIV positive women using conventional Pap smear. 2. To determine the association between various risk factors in HIV positive women and abnormal cytology on Pap smear. Design: A cross-sectional study was conducted in Bangalore Medical College in which eligible HIV-positive women underwent Pap smear, human papillomavirus (HPV) testing and cervical biopsy. Methods: Retropositive women attending gynaec OPD during the study period were taken into the study after taking informed consent. Women who fulfilled the inclusion criteria were subjected to Pap smear. Bethesda system of classification was used for reporting the Pap smear. Women with abnormal Pap smear were further evaluated by HPV DNA testing and cervical biopsy. Results: Cervical cytology was abnormal in 30% of the HIV-positive women, out of which 10% had HSIL, 15% had LSIL and 5% had ASCUS. Age at first sexual intercourse < 17 years (p = 0.009), past H/O STI (p = 0.0001), women with husband's having multiple sexual partners (p = 0.0001), women with CD4 count < 350 cells/micro-litre (p = 0.0001) were significant risk factors associated with abnormal Pap smear. Conclusion: Invasive cervical cancer is considered a preventable disease because of its long preinvasive state. Therefore, screening for premalignant cervical lesions represents an opportunity to prevent women developing cervical carcinoma.

3.
BMJ Open ; 11(10): e050571, 2021 10 04.
Artículo en Inglés | MEDLINE | ID: mdl-34607865

RESUMEN

OBJECTIVE: Large data on the clinical characteristics and outcome of COVID-19 in the Indian population are scarce. We analysed the factors associated with mortality in a cohort of moderately and severely ill patients with COVID-19 enrolled in a randomised trial on convalescent plasma. DESIGN: Secondary analysis of data from a Phase II, Open Label, Randomized Controlled Trial to Assess the Safety and Efficacy of Convalescent Plasma to Limit COVID-19 Associated Complications in Moderate Disease. SETTING: 39 public and private hospitals across India during the study period from 22 April to 14 July 2020. PARTICIPANTS: Of the 464 patients recruited, two were lost to follow-up, nine withdrew consent and two patients did not receive the intervention after randomisation. The cohort of 451 participants with known outcome at 28 days was analysed. PRIMARY OUTCOME MEASURE: Factors associated with all-cause mortality at 28 days after enrolment. RESULTS: The mean (SD) age was 51±12.4 years; 76.7% were males. Admission Sequential Organ Failure Assessment score was 2.4±1.1. Non-invasive ventilation, invasive ventilation and vasopressor therapy were required in 98.9%, 8.4% and 4.0%, respectively. The 28-day mortality was 14.4%. Median time from symptom onset to hospital admission was similar in survivors (4 days; IQR 3-7) and non-survivors (4 days; IQR 3-6). Patients with two or more comorbidities had 2.25 (95% CI 1.18 to 4.29, p=0.014) times risk of death. When compared with survivors, admission interleukin-6 levels were higher (p<0.001) in non-survivors and increased further on day 3. On multivariable Fine and Gray model, severity of illness (subdistribution HR 1.22, 95% CI 1.11 to 1.35, p<0.001), PaO2/FiO2 ratio <100 (3.47, 1.64-7.37, p=0.001), neutrophil lymphocyte ratio >10 (9.97, 3.65-27.13, p<0.001), D-dimer >1.0 mg/L (2.50, 1.14-5.48, p=0.022), ferritin ≥500 ng/mL (2.67, 1.44-4.96, p=0.002) and lactate dehydrogenase ≥450 IU/L (2.96, 1.60-5.45, p=0.001) were significantly associated with death. CONCLUSION: In this cohort of moderately and severely ill patients with COVID-19, severity of illness, underlying comorbidities and elevated levels of inflammatory markers were significantly associated with death. TRIAL REGISTRATION NUMBER: CTRI/2020/04/024775.


Asunto(s)
COVID-19 , Adulto , COVID-19/terapia , Humanos , Inmunización Pasiva , India/epidemiología , Persona de Mediana Edad , SARS-CoV-2 , Sueroterapia para COVID-19
4.
Oncotarget ; 12(20): 2051-2067, 2021 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-34611479

RESUMEN

Multiple Myeloma (MM) patients suffer disease relapse due to the development of therapeutic resistance. Increasing evidence suggests that immunotherapeutic strategies can provide durable responses. Here we evaluate the possibility of adoptive cell transfer (ACT) by generating ex vivo T cells from peripheral blood mononuclear cells (PBMCs) isolated from MM patients by employing our previously devised protocols. We designed peptides from antigens (Ags) including cancer testis antigens (CTAs) that are over expressed in MM. We exposed PBMCs from different healthy donors (HDs) to single peptides. We observed reproducible Ag-specific cluster of differentiation 4+ (CD4+) and CD8+ T cell responses on exposure of PBMCs to different single peptide sequences. These peptide sequences were used to compile four different peptide cocktails. Naïve T cells from PBMCs from MM patients or HDs recognized the cognate Ag in all four peptide cocktails, leading to generation of multiclonal Ag-specific CD4+ and CD8+ effector and central memory T (TEM and TCM, respectively) cells which produced interferon-gamma (IFN-γ), granzyme B and perforin on secondary restimulation. Furthermore, this study demonstrated that immune cells from MM patients are capable of switching metabolic programs to induce effector and memory responses. Multiple peptides and cocktails were identified that induce IFN-γ+, T1-type, metabolically active T cells, thereby paving the way for feasibility testing of ACT in phase I clinical trials.

5.
Phys Rev E ; 104(6-1): 064701, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35030859

RESUMEN

Two-dimensional liquid crystal (LC) models of interacting V-shaped bent-core molecules with two rigid rodlike identical segments connected at a fixed angle (θ=112^{∘}) are investigated. The model assigns equal biquadratic tensor coupling among constituents of the interacting neighboring molecules on a square lattice, allowing for reorientations in three dimensions (d=2, n=3). We find evidence of two temperature-driven topological transitions mediated by point disclinations associated with the three ordering directors, condensing the LC medium successively into uniaxial and biaxial phases. With Monte Carlo simulations, temperature dependencies of the system energy, specific heat, orientational order parameters, topological order parameters, and densities of unbound topological defects of the different ordering directors are computed. The high-temperature transition results in topological ordering of disclinations of the primary director, imparting uniaxial symmetry to the phase. The low-temperature transition precipitates simultaneous topological ordering of defects of the remaining directors, resulting in biaxial symmetry. The correlation functions, quantifying spatial variations of the orientational correlations of the molecular axes show exponential decays in the high-temperature (disordered) phase, and power-law decays in the low-temperature (biaxial) phase. Differing temperature dependencies of the topological parameters point to a significant degree of cross coupling among the uniaxial and biaxial tensors of interacting molecules. This simplified Hamiltonian leaves θ as the only free model parameter, and the system traces a θ-dependent trajectory in a plane of the phenomenological parameter space.

6.
Phys Rev E ; 102(4-1): 040701, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33212740

RESUMEN

Two-dimensional three-vector (d=2,n=3) lattice model of a liquid crystal (LC) system with order parameter space (R) described by the fundamental group Π_{1}(R)=Z_{2} was recently investigated based on non-Boltzmann Monte Carlo simulations. Its results indicated that the system did not undergo a topological transition condensing to a low temperature critical state as was reported earlier. Instead, a crossover to a nematic phase was observed, induced by the onset of a competing relevant length scale. This mechanism is further probed here by assigning a more restrictive R symmetry with Π_{1}(R)=Q (the discrete and non-Abelian group of quaternions), thus engaging the three spin degrees in the formation of point topological defects (disclinations). The results reported here indicate that such a choice of symmetry of the Hamiltonian with suitable model parameters leads to a defect-mediated transition to a low-temperature phase with topological order. It is characterized by a line of critical points with quasi-long-range order of its three spin degrees. The associated temperature-dependent power-law exponent decreases progressively and vanishes linearly as temperature tends to zero. The high-temperature disordered phase shows exponential spin correlations and their temperature-dependent lengths exhibit an essential singular divergence as the system approaches the topological transition point. Biaxial LC models have the required R symmetry owing to their tensor orientational orders and are suggested to serve as prototype examples to exhibit topological transition in (d=2,n=3) lattice models.

7.
Med Hypotheses ; 126: 60-65, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-31010501

RESUMEN

Every year millions of lacerations and incisions taken place and require an effective methodology to manage the wound for a better life. The primary causes include mechanical trauma and surgical procedures. The rapid healing of the wound is critical to prevent further infection and reduction pain etc. Current options comprise of sutures, staplers, surgical strips and glues, again the intervention depends on the type of wound and the surgeon preference. The current wound closure techniques pose various potent limitations and confronting the problems to create a desired wound closure technique is necessary for faster and effective wound healing management. The surgical staplers are fast and easy to use wound closure devices, which approximates the edges of the wounds together by staples. The staples are mostly made up of metals like titanium and stainless steel. By modifying the existing stapling method using biodegradable staples that are expected to have good mechanical properties, not require removal procedure, minimized scarring and an overall acceleration in wound healing with minimal complications. Present, the paper focuses on the novel hypothesis on natural fiber reinforced biodegradable polymer staples as wound enclosures with high strength and degradability.


Asunto(s)
Materiales Biocompatibles/química , Procedimientos Quirúrgicos Dermatologicos , Grapado Quirúrgico/métodos , Técnicas de Sutura/instrumentación , Suturas , Cicatrización de Heridas , Animales , Humanos , Modelos Teóricos , Polímeros/química , Infección de la Herida Quirúrgica , Heridas y Lesiones/terapia
8.
Phys Rev Lett ; 121(21): 217801, 2018 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-30517804

RESUMEN

The presence of stable topological defects in a two-dimensional (d=2) liquid crystal model allowing molecular reorientations in three dimensions (n=3) was largely believed to induce a defect-mediated Berzenskii-Kosterlitz-Thouless-type transition to a low temperature phase with quasi-long-range order. However, earlier Monte Carlo (MC) simulations could not establish certain essential signatures of the transition, suggesting further investigations. We study this model by computing its equilibrium properties through MC simulations, based on the determination of the density of states of the system. Our results show that, on cooling, the high temperature disordered phase deviates from its initial progression towards the topological transition, crossing over to a new fixed point, condensing into a nematic phase with exponential correlations of its director fluctuations. The thermally induced topological kinetic processes continue, however, limited to the length scales set by the nematic director fluctuations, and lead to a second topological transition at a lower temperature. It is argued that in the (d=2, n=3) system with an attractive biquadratic Hamiltonian, the presence of additional molecular degrees of freedom and local Z_{2} symmetry associated with lattice sites together promote the onset of an additional relevant scaling field at matching length scales in the high temperature region, leading to a crossover.

9.
Phys Rev E ; 96(3-1): 032703, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29346959

RESUMEN

General quadratic Hamiltonian models, describing the interaction between liquid-crystal molecules (typically with D_{2h} symmetry), take into account couplings between their uniaxial and biaxial tensors. While the attractive contributions arising from interactions between similar tensors of the participating molecules provide for eventual condensation of the respective orders at suitably low temperatures, the role of cross coupling between unlike tensors is not fully appreciated. Our recent study with an advanced Monte Carlo technique (entropic sampling) showed clearly the increasing relevance of this cross term in determining the phase diagram (contravening in some regions of model parameter space), the predictions of mean-field theory, and standard Monte Carlo simulation results. In this context, we investigated the phase diagrams and the nature of the phases therein on two trajectories in the parameter space: one is a line in the interior region of biaxial stability believed to be representative of the real systems, and the second is the extensively investigated parabolic path resulting from the London dispersion approximation. In both cases, we find the destabilizing effect of increased cross-coupling interactions, which invariably result in the formation of local biaxial organizations inhomogeneously distributed. This manifests as a small, but unmistakable, contribution of biaxial order in the uniaxial phase. The free-energy profiles computed in the present study as a function of the two dominant order parameters indicate complex landscapes. On the one hand, these profiles account for the unusual thermal behavior of the biaxial order parameter under significant destabilizing influence from the cross terms. On the other, they also allude to the possibility that in real systems, these complexities might indeed be inhibiting the formation of a low-temperature biaxial order itself-perhaps reflecting the difficulties in their ready realization in the laboratory.

10.
Oncotarget ; 8(7): 10785-10808, 2017 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-27974697

RESUMEN

Effective adoptive immunotherapy has proved elusive for many types of human cancer, often due to difficulties achieving robust expansion of natural tumor-specific T-cells from peripheral blood. We hypothesized that antigen-driven T-cell expansion might best be triggered in vitro by acute activation of innate immunity to mimic a life-threatening infection. Unfractionated peripheral blood mononuclear cells (PBMC) were subjected to a two-step culture, first synchronizing their exposure to exogenous antigens with aggressive surrogate activation of innate immunity, followed by γ-chain cytokine-modulated T-cell hyperexpansion. Step 1 exposure to GM-CSF plus paired Toll-like receptor agonists (resiquimod and LPS), stimulated abundant IL-12 and IL-23 secretion, as well as upregulated co-stimulatory molecules and CD11c expression within the myeloid (CD33+) subpopulation. Added synthetic long peptides (>20aa) derived from widely expressed oncoproteins (MUC1, HER2/neu and CMVpp65), were reliably presented to CD4+ T-cells and cross-presented to CD8+ T-cells. Both presentation and cross-presentation demonstrated proteasomal and Sec61 dependence that could bypass the endoplasmic reticulum. Step 2 exposure to exogenous IL-7 or IL-7+IL-2 produced selective and sustained expansion of both CD4+ and CD8+ peptide-specific T-cells with a predominant interferon-γ-producing T1-type, as well as the antigen-specific ability to lyse tumor targets. Other γ-chain cytokines and/or combinations were initially proliferogenic, but followed by a contractile phase not observed with IL-7 or IL-7+IL-2. Regulatory T-cells were minimally propagated under these culture conditions. This mechanistically rational culture sequence, effective even for unvaccinated donors, enables rapid preparation of T-cells recognizing tumor-associated antigens expressed by the majority of human cancers, including pancreatic cancers, breast cancers and glioblastomas.


Asunto(s)
Antígenos de Neoplasias/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Interleucina-7/farmacología , Mucina-1/inmunología , Receptor ErbB-2/inmunología , Antígenos de Neoplasias/metabolismo , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/metabolismo , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Reactividad Cruzada/inmunología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/inmunología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/farmacología , Humanos , Imidazoles/farmacología , Inmunidad Innata/efectos de los fármacos , Inmunidad Innata/inmunología , Inmunoterapia Adoptiva/métodos , Interferón gamma/inmunología , Interferón gamma/metabolismo , Interleucina-2/inmunología , Interleucina-2/farmacología , Interleucina-7/inmunología , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Lipopolisacáridos/inmunología , Lipopolisacáridos/farmacología , Activación de Linfocitos/efectos de los fármacos , Activación de Linfocitos/inmunología , Mucina-1/metabolismo , Neoplasias/inmunología , Neoplasias/terapia , Péptidos/inmunología , Péptidos/farmacología , Receptor ErbB-2/metabolismo , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo
11.
J Parasit Dis ; 40(4): 1401-1405, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27876957

RESUMEN

The dog tapeworm Echinococcusgranulosus is the causative agent of cystic hydatid disease in domestic/wild herbivores animals and man. Accurate immunodiagnosis of the infection requires highly specific and sensitive antigens. The aim of this study was to develop and evaluate immunoassays with principles of precipitation, agglutination for the identification of buffaloes infected with hydatid cyst which would allow the monitoring of animals from endemic areas and identifying infected animals prior to slaughter. The immunoassays were developed and validated using hydatid specific, non-cross reactive low molecular weight 8 kDa hydatid cyst fluid protein. Sera used for the assay validations were obtained from 200 buffaloes infected naturally with hydatid cyst and 200 non-infected buffaloes. The diagnostic sensitivity with latex agglutination test was 98.67 %. It should be useful for the conformation of hydatid cyst infected individual sheep.

12.
Biomolecules ; 6(3)2016 06 29.
Artículo en Inglés | MEDLINE | ID: mdl-27367740

RESUMEN

Cancer vaccines have often failed to live up to their promise, although recent results with checkpoint inhibitors are reviving hopes that they will soon fulfill their promise. Although mutation-specific vaccines are under development, there is still high interest in an off-the-shelf vaccine to a ubiquitous antigen, such as MUC1, which is aberrantly expressed on most solid and many hematological tumors, including more than 90% of breast carcinomas. Clinical trials for MUC1 have shown variable success, likely because of immunological tolerance to a self-antigen and to poor immunogenicity of tandem repeat peptides. We hypothesized that MUC1 peptides could be optimized, relying on heteroclitic optimizations of potential anchor amino acids with and without tumor-specific glycosylation of the peptides. We have identified novel MUC1 class I peptides that bind to HLA-A*0201 molecules with significantly higher affinity and function than the native MUC1 peptides. These peptides elicited CTLs from normal donors, as well as breast cancer patients, which were highly effective in killing MUC1-expressing MCF-7 breast cancer cells. Each peptide elicited lytic responses in greater than 6/8 of normal individuals and 3/3 breast cancer patients. The CTLs generated against the glycosylated-anchor modified peptides cross reacted with the native MUC1 peptide, STAPPVHNV, suggesting these analog peptides may offer substantial improvement in the design of epitope-based vaccines.


Asunto(s)
Vacunas contra el Cáncer , Antígeno HLA-A2 , Mucina-1 , Péptidos , Linfocitos T Citotóxicos/inmunología , Anciano , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/metabolismo , Femenino , Glicosilación , Antígeno HLA-A2/inmunología , Antígeno HLA-A2/metabolismo , Humanos , Tolerancia Inmunológica , Interferón gamma , Células MCF-7 , Persona de Mediana Edad , Mucina-1/inmunología , Mucina-1/metabolismo , Péptidos/inmunología , Péptidos/metabolismo
13.
Indian J Endocrinol Metab ; 20(3): 359-63, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27186554

RESUMEN

BACKGROUND: Assessment of cervical lymph node involvement in patients with thyroid cancer either during preoperative surgical mapping or detection of recurrences during follow-up is a crucial step in the management of differentiated thyroid cancers (DTCs). In most patients, fine needle aspiration cytology (FNAC) confirms the presence of metastasis in lymph node. However, in cases of paucicellular lymph node aspirate or discordant sonogram and cytology results, thyroglobulin (Tg) measurement in the lymph node aspirate (FNA-Tg) is useful and a value >1 ng/ml is considered consistent with metastatic disease. CONTEXT: The addition of FNAC to the US improves the specificity, but 5-10% are nondiagnostic and 6-8% rate of false-negative results. Several studies have reported that the detection of Tg in FNA-needle washes improves the evaluation of suspicious lymph nodes in patients with DTC.Data from Indian centers on FNA-Tg are limited. AIMS: We piloted the utility of FNA-Tg in patients with sonographically suspicious cervical lymph node enlargement in the setting of suspicious thyroid nodule or in the follow-up of thyroid cancer. SETTINGS AND DESIGN: Prospective data collection. RESULTS: We measured Tg in 13 lymph node aspirates (12 patients, 10 females) among whom 4 patients had a total thyroidectomy and 1 had a hemithyroidectomy. Eight of the 13 lymph node aspirates had FNA-Tg values >150 ng/ml, all of them had unequivocal malignant cytology and four among them had proven metastatic DTC on surgical pathology. The median FNA-Tg of the patients with malignant cytology was 7550 ng/ml with a range of 162-30,000 ng/ml. Among the remaining 5 lymph node aspirate, 2 lymph nodes showed cytological features suggestive of reactive lymphadenitis (FNA-Tg <0.2 ng/ml) and were not operated, 1 had a high-grade malignancy consistent with anaplastic thyroid cancer (FNA-Tg <0.2 ng/ml), and 2 had nondiagnostic cytology (one had non-caseating granuloma on surgical pathology [FNA-Tg 1.3 ng/ml] and in the other patient [FNA-Tg <0.2 ng/ml] surgical intervention was deferred). CONCLUSIONS: FNA-Tg was concordant with positive cytology in all patients with DTC and may serve as a useful tool in patients with negative and nondiagnostic cytology to guide surgical management.

14.
PLoS One ; 11(1): e0145920, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26788922

RESUMEN

It remains challenging to produce decisive vaccines against MUC1, a tumor-associated antigen widely expressed by pancreas, breast and other tumors. Employing clinically relevant mouse models, we ruled out such causes as irreversible T-cell tolerance, inadequate avidity, and failure of T-cells to recognize aberrantly glycosylated tumor MUC1. Instead, every tested MUC1 preparation, even non-glycosylated synthetic 9mer peptides, induced interferon gamma-producing CD4(+) and CD8(+) T-cells that recognized glycosylated variants including tumor-associated MUC1. Vaccination with synthetic peptides conferred protection as long as vaccination was repeated post tumor challenge. Failure to revaccinate post challenge was associated with down-regulated tumor MUC1 and MHC molecules. Surprisingly, direct admixture of MUC1-expressing tumor with MUC1-hyperimmune T-cells could not prevent tumor outgrowth or MUC1 immunoediting, whereas ex vivo activation of the hyperimmune T-cells prior to tumor admixture rendered them curative. Therefore, surrogate T-cell preactivation outside the tumor bed, either in culture or by repetitive vaccination, can overcome tumor escape.


Asunto(s)
Vacunas contra el Cáncer/uso terapéutico , Mucina-1/genética , Mucina-1/inmunología , Neoplasias Experimentales/prevención & control , Péptidos/uso terapéutico , Animales , Antígenos/química , Antígenos/inmunología , Antígenos/uso terapéutico , Vacunas contra el Cáncer/química , Vacunas contra el Cáncer/inmunología , Línea Celular Tumoral , Glicosilación , Humanos , Ratones , Ratones Transgénicos , Mucina-1/metabolismo , Neoplasias Experimentales/inmunología , Péptidos/química , Péptidos/inmunología , Linfocitos T/inmunología , Linfocitos T/metabolismo , Escape del Tumor
15.
J Parasit Dis ; 39(3): 401-4, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26345041

RESUMEN

The occurrence of the pentastomid Porocephalus crotali in an Indian rat snake (Ptyas mucosus) at Chennai, India is reported. The worms were found in the lungs and they were identified as females. The worms were cylindrical and annulated with a centrally located mouth surrounded by four hooks. The worms were rounded in cross section with tapering ends. Eggs were composed of two shell membranes. This is one of the new reports from rat snakes in Southern India.

16.
Artículo en Inglés | MEDLINE | ID: mdl-26274193

RESUMEN

Investigations of the phase diagram of biaxial liquid-crystal systems through analyses of general Hamiltonian models within the simplifications of mean-field theory (MFT), as well as by computer simulations based on microscopic models, are directed toward an appreciation of the role of the underlying molecular-level interactions to facilitate its spontaneous condensation into a nematic phase with biaxial symmetry. Continuing experimental challenges in realizing such a system unambiguously, despite encouraging predictions from MFT, for example, are requiring more versatile simulational methodologies capable of providing insights into possible hindering barriers within the system, typically gleaned through its free-energy dependences on relevant observables as the system is driven through the transitions. The recent paper from this group [Kamala Latha et al., Phys. Rev. E 89, 050501(R) (2014)], summarizing the outcome of detailed Monte Carlo simulations carried out employing an entropic sampling technique, suggested a qualitative modification of the MFT phase diagram as the Hamiltonian is asymptotically driven toward the so-called partly repulsive regions. It was argued that the degree of (cross) coupling between the uniaxial and biaxial tensor components of neighboring molecules plays a crucial role in facilitating a ready condensation of the biaxial phase, suggesting that this could be a plausible factor in explaining the experimental difficulties. In this paper, we elaborate this point further, providing additional evidence from curious variations of free-energy profiles with respect to the relevant orientational order parameters, at different temperatures bracketing the phase transitions.

17.
J Parasit Dis ; 39(1): 90-3, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25698868

RESUMEN

Cell mediated immune response to immunoaffinity chromatography purified midgut antigen of Rhipicephalus haemaphysaloides ticks in rabbits was studied by using lymphocyte transformation test. This test was carried out by using 5-bromo-2'-deoxy-uridine kit method. The blastogenic response of peripheral blood lymphocytes of normal rabbit to different concentrations of antigen and mitogen (Con A) showed that 2 µg of antigen and 2 µg of mitogen gave maximum stimulation index. The antigen specific responsiveness of immunized rabbits with affinity purified 35 kDa midgut antigen was highly significant (P ≤ 0.01) compared to mitogen. The maximum lymphocyte stimulation index (LSI) of 2.47 was observed on 49 day post immunization in immunized group. The lymphocytes separated from control animal cultured in RPMI1640 medium with 2 µg of antigen and 2 µg of mitogen (Con A) were never stimulated and their LSI values were below 2.0.

18.
Artículo en Inglés | MEDLINE | ID: mdl-25353730

RESUMEN

We investigate the phase sequence of biaxial liquid crystals, based on a general quadratic model Hamiltonian over the relevant parameter space, with a Monte Carlo simulation which constructs equilibrium ensembles of microstates, overcoming possible (free) energy barriers (combining entropic and frontier sampling techniques). The resulting phase diagram qualitatively differs from the universal phase diagram predicted earlier from mean-field theory (MFT), as well as the Monte Carlo simulations with the Metropolis algorithm. The direct isotropic-to-biaxial transition predicted by the MFT is replaced in certain regions of the space by the onset of an additional intermediate biaxial phase of very low order, leading to the sequence N(B)-N(B1)-I. This is due to inherent barriers to fluctuations of the components comprising the total energy, and may explain the difficulties in the experimental realization of these phases.

19.
J Parasit Dis ; 38(4): 394-5, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25320490

RESUMEN

The occurrence of the plerocercoid larva, Sparganum of Sparganum spp. in two Russell's viper snakes maintained in Chennai snake park trust, Chennai is reported for the first time from Southern India. The cestode larvae were found in the sub cutis and were flat, solid, wrinkled, ribbon like creamy white in colour with peudosegmentation with anterior end possessing bothria. The cuticles, subcuticular cells and parenchymatous tissue stained by acetic alum carmine further confirmed the cestode larvae.

20.
J Parasit Dis ; 38(3): 260-4, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25035581

RESUMEN

Tick gut glycoprotein, designated as Bm86, found on the luminal surface of the plasma membrane of gut epithelial cells of Boophilus microplus, which is a concealed antigen, has been used as vaccine candidate molecule for immunization against ticks. To better understand the molecular diversity of Bm86 gene in ticks, a portion of the cDNA was sequenced from an Indian isolate of B. microplus. Comparison of nucleotide sequence revealed that Indian isolate had 97 % homology (18 polymorphisms) with that of the Australian isolate and 96 % homology (20 polymorphisms) with that of the Cuban vaccine strain. Further, the Indian isolate differed from the Cuban vaccine isolate at 7 amino acid loci, including 5 substitutions (at residues 88, 94, 175, 176 and 177) and 2 deletions (at 183 and 184). However, protein prediction studies did not show any difference in the putative antigenic epitopes of the protein expressed.

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