Increased Production of Interferon‐γ by Leishmania Homologue of the Mammalian Receptor for Activated C Kinase‐Reactive CD4+ T cells among Human Blood Mononuclear Cells: An Early Marker of Exposure to Leishmania?

A prospective study was undertaken to define early predictive immunological marker(s) of exposure to Leishmania in naïve subjects who have never been exposed to any Leishmania and who were also free of any cutaneous leishmaniasis lesions. These naïve subjects could have been exposed to Leishmania in a rain forest where Leishmania guyanensis and their natural vectors and mammalian host are cocirculating. The production of interferon (IFN)‐γ in response to the Leishmania homologue of the mammalian receptor for activated c kinase (LACK), a candidate for vaccine against leishmaniasis was analysed. At the end of their stay in the rain forest, LACK‐specific CD8⁺ T cells were detected in subjects whose peripheral blood mononuclear cell (PBMC) produced IFN‐γ in response to soluble Leishmania antigens (SLA) and in those whose PBMC remained unresponsive to SLA. However, LACK‐specific CD4⁺ T cells were detected only in PBMCs from individuals who became IFN‐γ responders to SLA. In subjects whose PBMC became positive to SLA, LACK‐reactive CD4⁺ T cells producing high level of IFN‐γ were detectable before the SLA‐reactive IFN‐γ producing CD4⁺ T cells, suggesting that the former readout assay could be used as an early predictive immunological marker of exposure to Leishmania in subjects who remained disease free.     

Quality-of-Life Measurements in Multiethnic Patients with Systemic Lupus Erythematosus: Cross-Cultural Issues

Although the survival rate for systemic lupus erythematosus (SLE) has improved dramatically during the past 50 years, the quality of life of patients afflicted with this disease remains poor. Currently existent measures of disease activity and damage in SLE do not capture the patient’s perspective and health-related quality of life (HRQoL). Most studies in SLE pertaining to HRQoL are from developed Western societies, with only a few from others. These studies have been conducted predominantly in women and using the Medical Outcomes Survey Short Form 36, a generic HRQoL instrument that has been shown not to be sensitive to change in lupus. Existent lupus-specific HRQoL measures have not yet been used in SLE clinical trials. New HRQoL research tools are currently undergoing validation in different countries, languages, and cultural settings, which may help dissect the underlying role of socioeconomic status and specific disease-related features that impact SLE-related quality of life.     

Mapping of cerebral oxidative metabolism with MRI

Using a T_1ρ MRI based indirect detection method, we demonstrate the detection of cerebral oxidative metabolism and its modulation by administration of the mitochondrial uncoupling agent 2,4-dinitrophenol (DNP) in a large animal model with minimum utilization of gas. The study was performed by inhalation in swine during imaging on clinical MRI scanners. Metabolic changes in swine were determined by two methods. First, in a series of animals, increased metabolism caused by DNP injection was measured by exhaled gas analysis. The average whole-body metabolic increase in seven swine was 11.9%+/-2.5% per mg/kg, stable over three hours. Secondly, hemispheric brain measurements of oxygen consumption stimulated by DNP injection were made in five swine using T_1ρ MRI following administration of gas. Metabolism was calculated from the change in the T_1ρ weighted MRI signal due to H₂¹⁷O generated from inhalation before and after doubling of metabolism by DNP. These results were confirmed by direct oxygen-17 MR spectroscopy, a gold standard for in vivo H₂¹⁷O measurement. Overall, this work underscores the ability of indirect oxygen-17 imaging to detect oxygen metabolism in an animal model with a lung capacity comparable to the human with minimal utilization of expensive gas. Given the demonstrated high efficiency in use of and the proven feasibility of performing such measurements on standard clinical MRI scanners, this work enables the adaption of this technique for human studies dealing with a broad array of metabolic derangements.     

Long-term effects of laparoscopic sleeve gastrectomy in morbidly obese subjects with type 2 diabetes mellitus

BackgroundLaparoscopic sleeve gastrectomy (LSG) is becoming popular as a stand-alone procedure for the treatment of morbid obesity and related diseases. This retrospective study presents the outcomes of LSG with regard to weight loss and improvement in co-morbidities and quality of life (QOL) at the end of 3 years after surgery in a tertiary care hospital in Pune, India.MethodsA total of 23 patients with type 2 diabetes mellitus (6 men and 17 women) with morbid obesity (mean body mass index 40.7 ± 6.6 kg/m²) who had undergone LSG from 2004 to 2005 were selected for the present analysis. The percentage of excess weight loss and changes in co-morbidity status and QOL at the end of 3 years were calculated. The patients were simultaneously evaluated using the Bariatric Analysis and Reporting Outcome System scores. P values <.05 were considered significant.ResultsAt 36 months after surgery, the percentage of excess weight loss was 74.58%, a significant number of patients (16 of 23, P <.05) had had improvement in all co-morbidities, and 7 showed improvement in ≥1 co-morbidity. All patients indicated improvement in their QOL but not equally for all parameters included in the questionnaire. The Bariatric Analysis and Reporting Outcome System score was good in 4, very good in 4, and excellent in 15 of the 23 patients.ConclusionOur data have shown that LSG is a highly effective and safe procedure for achieving weight loss, improving co-morbidities, and improving the QOL in patients with type 2 diabetes mellitus and morbid obesity during a long-term period.     

Fetal habituation in assisted conception

Background

Neurodevelopment outcomes of children conceived by Assisted Reproductive Technology (ART)have been the subject of much recent attention. To date there are no reports of neurodevelopmental performance before birth in this group.

Aims

To compare habituation (a measure of brain function) in fetuses conceived by assisted reproduction techniques (ART) with naturally conceived (NC) fetuses.

Study design

Case control study.

Subjects

Women with singleton pregnancies matched for maternal age, parity and smoking were recruited in 2 groups: ART (n = 20) and NC (n = 20).

Outcome measures

Sound stimuli (250 Hz, 110 dB) at 10 second intervals lasting 2 s were administered to the fetus. The end point was habituation (cessation of movement for five consecutive stimuli) or a maximum of 30 stimuli. Responses of the fetus were observed with ultrasound at 28, 32 and 36 weeks' gestation, video-recorded and anonymised for analysis.

Results

At 28 weeks' gestation significantly more ART fetuses responded to sound of 250 Hz, 110 dB (p = 0.02) but this difference did not persist at 32 and 36 weeks'. There was a significant increase in nonresponders as gestation advanced in the ART group. There was no difference in habituation or mean number of trials to habituate at all three gestations.

Conclusions

ART fetuses demonstrated no differences in habituation suggesting that there is no neurodevelopment delay. However, a decrease in response to sound as gestation advances might be a harbinger for poor perinatal outcomes and needs exploration.     

A 6-year experience of 100 cases of pediatric bony craniovertebral junction abnormalities: treatment and outcomes

The authors studied 100 consecutive cases of pediatric bony craniovertebral junction abnormalities operated between 2001 and 2006. The pathologies were developmental (n = 86), traumatic (n = 10) and tuberculous (n = 4). Surgical procedures included transoral decompression (n = 59), occipitocervical fusion (OCF, n = 69), C(1)-C(2) fusion (n = 22), occiput-C(2) wiring (n = 5), and posterior fossa decompression (n = 5). Implants for OCF included contoured stainless steel rods (n = 47), titanium lateral mass screws and plates (n = 16) and steel wires (n = 5). Adequate bone fusion was observed in all patients with OCF at a mean follow-up of 16.5 months, irrespective of the type of implant used for posterior fixation. Good neurological outcome was observed even in poor-grade patients. No significant effect on the curvature or growth of the spine was observed at follow-up.     

α7 Nicotinic Acetylcholine Receptor Regulates Airway Epithelium Differentiation by Controlling Basal Cell Proliferation

Airway epithelial basal cells are known to be critical for regenerating injured epithelium and maintaining tissue homeostasis. Recent evidence suggests that the α7 nicotinic acetylcholine receptor (nAChR), which is highly permeable to Ca²⁺, is involved in lung morphogenesis. Here, we have investigated the potential role of the α7 nAChR in the regulation of airway epithelial basal cell proliferation and the differentiation of the human airway epithelium. In vivo during fetal development and in vitro during the regeneration of the human airway epithelium, α7 nAChR expression coincides with epithelium differentiation. Inactivating α7 nAChR function in vitro increases cell proliferation during the initial steps of the epithelium regeneration, leading to epithelial alterations such as basal cell hyperplasia and squamous metaplasia, remodeling observed in many bronchopulmonary diseases. The regeneration of the airway epithelium after injury in α7^−/− mice is delayed and characterized by a transient hyperplasia of basal cells. Moreover, 1-year-old α7^−/− mice more frequently present basal cells hyperplasia. Modulating nAChR function or expression shows that only α7 nAChR, as opposed to heteropentameric α_xβ_y nAChRs, controls the proliferation of human airway epithelial basal cells. These findings suggest that α7 nAChR is a key regulator of the plasticity of the human airway epithelium by controlling basal cell proliferation and differentiation pathway and is involved in airway remodeling during bronchopulmonary diseases.The respiratory epithelium, which is constantly exposed to airborne pollutants, is frequently injured, which results in altered epithelial functions. To restore these functions, the respiratory epithelium must undergo rapid repair via epithelial cell spreading and migration and regenerate its structure via basal cell proliferation and differentiation.¹ These processes are tightly controlled to restore the pseudostratified architecture of the normal mucociliary epithelium. However, in most respiratory diseases, alterations of the regeneration processes induce epithelial remodeling such as hyperplasia, metaplasia, and fibrosis. Understanding the sequence of processes involved in cell proliferation and differentiation is therefore of crucial importance. Both in vivo and in vitro, human airway basal cells are able to proliferate and reconstitute a fully differentiated and functional epithelium.² These cells are such considered as progenitors of the human airway epithelium and important actors of the airway epithelium regeneration.The nonneuronal cholinergic system is thought to be involved in the regulation of cell functions such as cell-cell interaction, apoptosis, and proliferation.³ It is now established that human bronchial epithelial cells contain all of the machinery for the production, storage, secretion, and degradation of acetylcholine, which acts as an autocrine or paracrine hormone.^4,5 Acetylcholine exerts its effects through muscarinic and nicotinic acetylcholine receptors. Nicotinic acetylcholine receptors (nAChRs) are composed of five subunits, arranged as α/β heteromeric or α homomeric nAChRs, and assembled around a central ion channel, mediating the influx of Ca²⁺.⁶ The airway epithelium expresses α3, α4, α5, α7, α9, β2, and β4 subunits for nAChRs.^7,8,9α7 nAChR is characterized by an elevated Ca²⁺ permeability¹⁰ and has been involved in several important biological processes such as cell proliferation, apoptosis, and angiogenesis in cancer.^11,12 Prenatal nicotine exposure significantly increases pulmonary α7 nAChR expression and alters fetal lung development¹³ and subsequently pulmonary function in newborn.¹⁴ In particular, alteration of lung branching morphogenesis induced by nicotine is mediated by α7 nAChR.¹⁵ Altogether, these observations led us to investigate whether the α7 nAChR could be involved in the differentiation of the respiratory epithelium. In the human airway epithelium, we observed α7 nAChR expression in basal cells, which play a critical role in the epithelial regeneration. Both in vivo and in vitro, the α7 nAChR expression is associated with the airway epithelium differentiation. Moreover, in vitro inactivating α7 nAChR or in vivo disrupting genetic α7 nAChR expression induces airway epithelium remodeling by modulating basal cell proliferation. This study thus provides several lines of evidence that α7 nAChR is significant for airway epithelial differentiation and suggests that α7 nAChR is a key regulator of the plasticity of the airway epithelium.     

Effect of lipoarabinomannan from Mycobacterium avium subsp avium in Freund's incomplete adjuvant on the immune response of cattle

The aim of the present study was to determine whether lipoarabinomannan (LAM), in combination with Freund''s incomplete adjuvant (FIA), was able to improve cell-mediated and antibody-mediated immune responses against ovalbumin (OVA) in cattle. Twenty-three calves were assigned to four treatment groups, which were subcutaneously immunized with either OVA plus FIA, OVA plus FIA and LAM from Mycobacterium avium subsp avium, FIA plus LAM, or FIA alone. Lymphoproliferation, IFN-γ production and cell subpopulations on peripheral blood mononuclear cells before and 15 days after treatment were evaluated. Delayed hypersensitivity was evaluated on day 57. Specific humoral immune response was measured by ELISA. Inoculation with LAM induced higher levels of lymphoproliferation and IFN-γ production in response to ConA and OVA (P < 0.05). Specific antibody titers were similar in both OVA-immunized groups. Interestingly, our results showed that the use of LAM in vaccine preparations improved specific cell immune response evaluated by lymphoproliferation and IFN-γ production by at least 50 and 25%, respectively, in cattle without interfering with tuberculosis and paratuberculosis diagnosis.