Selective DNAM-1 expression on small peritoneal macrophages contributes to CD4+ T cell costimulation.

Mouse peritoneal macrophages consist of two subsets: large peritoneal macrophages (LPMs) and small peritoneal macrophages (SPMs), defined as CD11bhiF4/80hi and CD11b+F4/80lo cells, respectively. We reveal that SPMs, but not LPMs, have the ability to present antigens to naïve CD4+ T cells. Coculture of SPMs with naïve ovalbumin (OVA) specific CD4+ T cells (OT-II) in the presence of OVA peptide effectively induced CD4+ T cells priming. SPMs, but not LPMs, strongly express DNAM-1, an activating immunoreceptor. Although antigen uptake and processing were comparable between WT and DNAM-1-deficient SPMs, deficiency of DNAM-1 on SPMs or blockade of DNAM-1 and its ligand interaction impaired CD4+ T cells priming by SPMs. Furthermore, T and B cell responses in mediastinal lymph nodes of mice intraperitoneally immunized with trinitrophenyl (TNP)-OVA protein in Alum adjuvant were enhanced by intraperitoneally transferred wild-type, but not DNAM-1-deficient, SPMs. We propose that SPMs are functionally distinct from LPMs, and DNAM-1 plays a costimulatory role in antigen presentation by SPMs.

Cross calibration of 123I-meta-iodobenzylguanidine heart-to-mediastinum ratio with D-SPECT planogram and Anger camera.

BACKGROUND: Cardiac 123I-meta-iodobenzylguanidine (MIBG) uptake is quantified using the heart-to-mediastinum ratio (HMR) with an Anger camera. The relationship between HMR determined using D-SPECT with a cadmium-zinc-telluride detector and an Anger camera is not fully understood. Therefore, the present study aimed to define this relationship using images derived from a phantom and from patients. METHODS: Cross-calibration phantom studies using an Anger camera with a low-energy high-resolution (LEHR) collimator and D-SPECT, and clinical 123I-MIBG studies proceeded in 40 consecutive patients (80 studies). In the phantom study, a conversion coefficient (CC) was defined based on phantom experiments and applied to the Anger camera and the D-SPECT detector. The HMR was calculated using anterior images with the Anger camera and anterior planograms with D-SPECT. First, the HMR from D-SPECT was cross-calibrated to the Anger camera, and then, the HMR from both cameras were converted to the medium-energy general-purpose collimator condition (CC 0.88; ME88 condition). The relationship between HMR and corrected and uncorrected methods was examined. A 123I-MIBG washout rate was calculated using both methods with and without background subtraction. RESULTS: Based on the phantom experiments, the CC of the Anger camera with an LEHR collimator and of D-SPECT using an anterior planogram was 0.55 and 0.63, respectively. The original HMR from the Anger camera and D-SPECT was 1.76 ± 0.42 and 1.86 ± 0.55, respectively (p < 0.0001). After D-SPECT HMR was converted to the Anger camera condition, the corrected D-SPECT HMR became comparable to the values under the Anger camera condition (1.75 ± 0.48, p = n. s.). When the HMR measured using the two cameras were converted under the ME88 condition, the average standardized HMR from the Anger camera and D-SPECT became comparable (2.21 ± 0.65 vs. 2.20 ± 0.75, p = n. s.). After standardization to the ME88 condition, a systematic difference in the linear regression lines disappeared, and the HMR from both the Anger (StdHMRAnger) and D-SPECT (StdHMRDSPECT) became comparable. Additional correction using a regression line further improved the relationship between both HMR [StdHMRDSPECT = 0.09 + 0.98 × StdHMRAnger (R 2 = 0.91)]. The washout rate closely correlated with and without background correction between both methods (R 2 = 0.83 and 0.65, respectively). CONCLUSION: The phantom-based conversion method is applicable to D-SPECT and enables the common application of HMR irrespective of D-SPECT and the Anger camera.

Descending necrotizing mediastinitis: Systematic review on its treatment in the last 6 years, 75 years after its description.

BACKGROUND: Descending necrotizing mediastinitis is a serious infection involving the neck and the chest, in which an odontogenic, pharyngeal, or cervical infection spreads rapidly to the thoracic cavity, with a high death rate by sepsis and organic failure if not treated quickly and properly. METHODS: A systematic search in the electronic database PubMed was conducted using the keywords "mediastinitis" and "descending necrotizing mediastinitis" resulting in 2560 items, filters were activated (systematic review, meta-analysis, and clinical trial) resulting in 60 articles, from which we selected relevant articles on the topic. RESULTS: The best available evidence we could obtain was from 26 case series with evidence level III. The overall mortality in this period was 17.5%. CONCLUSION: For mediastinitis limited to the upper part of the mediastinum, transcervical drainage may be sufficient; cases that extended below the tracheal carina may require cervical and transthoracic drainage. A multidisciplinary therapeutic approach has allowed a reduction in its mortality. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2275-E2283, 2016.

The potential of GMP-compliant platelet lysate to induce a permissive state for cardiovascular transdifferentiation in human mediastinal adipose tissue-derived mesenchymal stem cells.

Human adipose tissue-derived mesenchymal stem cells (ADMSCs) are considered eligible candidates for cardiovascular stem cell therapy applications due to their cardiac transdifferentiation potential and immunotolerance. Over the years, the in vitro culture of ADMSCs by platelet lysate (PL), a hemoderivate containing numerous growth factors and cytokines derived from platelet pools, has allowed achieving a safe and reproducible methodology to obtain high cell yield prior to clinical administration. Nevertheless, the biological properties of PL are still to be fully elucidated. In this brief report we show the potential ability of PL to induce a permissive state of cardiac-like transdifferentiation and to cause epigenetic modifications. RTPCR results indicate an upregulation of Cx43, SMA, c-kit, and Thy-1 confirmed by immunofluorescence staining, compared to standard cultures with foetal bovine serum. Moreover, PL-cultured ADMSCs exhibit a remarkable increase of both acetylated histones 3 and 4, with a patient-dependent time trend, and methylation at lysine 9 on histone 3 preceding the acetylation. Expression levels of p300 and SIRT-1, two major regulators of histone 3, are also upregulated after treatment with PL. In conclusion, PL could unravel novel biological properties beyond its routine employment in noncardiac applications, providing new insights into the plasticity of human ADMSCs.

Multicenter cross-calibration of I-123 metaiodobenzylguanidine heart-to-mediastinum ratios to overcome camera-collimator variations.

BACKGROUND: The heart-to-mediastinum ratio (HMR) of (123)I-metaiodobenzylguanidine (MIBG) showed variations among institutions and needs to be standardized among various scinticamera-collimator combinations. METHODS: A total of 225 phantom experiments were performed in 84 institutions to calculate cross-calibration coefficients of HMR. Based on phantom studies, a conversion coefficient for each camera-collimator system was created, including low-energy (LE, n = 125) and a medium-energy (ME, n = 100) collimators. An average conversion coefficient from the most common ME group was used to calculate the standard HMR. In clinical MIBG studies (n = 52) from three institutions, HMRs were standardized from both LE- and ME-type collimators and classified into risk groups of <1.60, 1.60-2.19, and ≥2.20. RESULTS: The average conversion coefficients from the individual camera-collimator condition to the mathematically calculated reference HMR ranged from 0.55 to 0.75 for LE groups and from 0.83 to 0.95 for ME groups. The conversion coefficient of 0.88 was used to unify HMRs from all acquisition conditions. Using the standardized HMR, clinical studies (n = 52) showed good agreement between LE and ME types regarding three risk groups (κ = 0.83, P < .0001, complete agreement in 90%, 42% of the patients reclassified into the same risk group). CONCLUSION: By using the reference HMR and conversion coefficients for the system, HMRs with various conditions can be converted to the standard HMRs in a range of normal to low HMRs.

The chest and aging: radiological findings.

In the elderly (conventionally defined as individuals ≥ 60 years of age), it is often difficult to establish what normality is, because of the numerous anatomical and physiological modifications that occur during the aging process. As a result, the greatest challenge is to differentiate between the normal aging process and the onset of disease. Healthy elderly people commonly present borderline findings on chest imaging. We systematically reviewed the medical literature on the subject, covering the period between 1950 and 2011, including articles in Portuguese, English, French, Italian, and Spanish. We searched the PubMed, LILACS, and SciELO databases, using the search terms "age", "aging", "lung", "thorax", "chest", "X-ray", "radiography", "pulmonary", and "computed tomography"-as well as their corresponding translations-in various combinations. We included only original or review articles on aging-related chest imaging findings. In broad terms, aging results in physiological modifications that must be recognized so as not to be erroneously interpreted as pathological.

O tórax e o envelhecimento: manifestações radiológicas / The chest and aging: radiological findings

Nos idosos (convencionalmente definidos como indivíduos com idade > de 60 anos), é muitas vezes difícil estabelecer o que é normal devido a inúmeras modificações anatômicas e fisiológicas que ocorrem durante o processo de envelhecimento. Como resultado, o principal problema consiste em diferenciar o ponto em que o envelhecimento é normal daquele no qual a doença começa. Os achados radiológicos do tórax de pessoas idosas sadias são comumente limítrofes. Revisamos sistematicamente a literatura médica sobre o assunto, abrangendo o período entre 1950 e 2011, incluindo artigos em português, inglês, francês, italiano e espanhol. A busca foi feita através das bases de dados PubMed, LILACS e SciELO, utilizando os seguintes termos: age, aging, lung, thorax, chest, X-ray, radiography, pulmonary, computed tomography e suas traduções correspondentes, em combinações variadas. Os critérios de inclusão foram artigos originais e de revisão de achados radiológicos no tórax relacionados ao envelhecimento. Em linhas gerais, o envelhecimento resulta em modificações fisiológicas que devem ser reconhecidas de forma a não serem erroneamente interpretadas como patologias.

In the elderly (conventionally defined as individuals > 60 years of age), it is often difficult to establish what normality is, because of the numerous anatomical and physiological modifications that occur during the aging process. As a result, the greatest challenge is to differentiate between the normal aging process and the onset of disease. Healthy elderly people commonly present borderline findings on chest imaging. We systematically reviewed the medical literature on the subject, covering the period between 1950 and 2011, including articles in Portuguese, English, French, Italian, and Spanish. We searched the PubMed, LILACS, and SciELO databases, using the search terms "age", "aging", "lung", "thorax", "chest", "X-ray", "radiography", "pulmonary", and "computed tomography"-as well as their corresponding translations-in various combinations. We included only original or review articles on aging-related chest imaging findings. In broad terms, aging results in physiological modifications that must be recognized so as not to be erroneously interpreted as pathological.

Cardiac sympathetic imaging with mIBG in cirrhosis and portal hypertension: relation to autonomic and cardiac function.

Autonomic and cardiac dysfunction is frequent in cirrhosis and includes increased sympathetic nervous activity, impaired heart rate variability (HRV), and baroreflex sensitivity (BRS). Quantified (123)I-metaiodobenzylguanidine (mIBG) scintigraphy reflects cardiac noradrenaline uptake, and in patients with cardiac failure it predicts outcome. In this study, we aimed to investigate cardiac sympathetic neuronal function in cirrhosis by mIBG scintigraphy in relation to cardiovascular function. Ten patients with alcoholic cirrhosis and 10 age- and sex-matched healthy controls participated in the study. Heart/mediastinum (H/M) ratios of mIBG uptake were calculated 15 and 230 min after intravenous injection of mIBG. Furthermore, washout rate (WOR) of mIBG was calculated. The patients underwent a liver vein catheterization with determination of splanchnic and systemic hemodynamics and measurement of HRV and BRS. mIBG-scintigraphy revealed significantly increased WOR in patients with cirrhosis compared with controls (P < 0.005), whereas H/M uptakes were equal in the groups. Forty percent of the patients had reduced uptake of mIBG in the infero-lateral segment of the left ventricle. WOR correlated significantly with central circulation time, an estimate of central hypovolemia (r = -0.64, P < 0.05) and frequency-corrected QT(F) interval (r = 0.71, P = 0.01). Patients with cirrhosis had significantly decreased HRV and BRS correlating with indicators of abnormal cathecholamine uptake by mIBG although the catecholamine level was normal in the patients. In conclusion, in alcoholic cirrhosis, mIBG scintigraphy reveals autonomic dysfunction and impaired myocardial distribution of sympathetic nervous activity. It is associated to indicators of central hypovolemia, QT interval, and decreased HRV and BRS. Measurement of myocardial catecholamine uptake by mIBG may add important information on autonomic and cardiac dysfunction in cirrhosis.

Role of the mediastinum in the mechanics of the canine diaphragm.

The objective of this study was to evaluate the role of the mediastinum in the mechanics of the canine diaphragm. Two sets of experiments were performed. In the first experiment on five animals, the mediastinum was severed from the sternum to the vena cava, and radiopaque markers were attached to muscle bundles in the midcostal region of the diaphragm. The three-dimensional location of the markers during relaxation at different lung volumes and during phrenic nerve stimulation at the same lung volumes was then measured using computed tomography. From these data, accurate measurements of muscle displacement and muscle length were obtained, and these measurements, together with the changes in airway opening pressure, were compared with those previously obtained in animals with an intact mediastinum. Severing the mediastinum per se appeared to have no influence on the pressure-generating capacity of the diaphragm or on the lung-volume dependence of this capacity. The great vessels and the esophagus in these animals, however, were left intact, so the possibility remained that these structures continued to impact on the diaphragm through their close attachments to the muscle. In the second experiment, therefore, loads were applied caudally to the central tendon to assess the force-displacement relationship of the entire mediastinum, and this relationship, combined with the known displacement of the diaphragm dome during phrenic nerve stimulation, was used to infer the force exerted by the mediastinum on the muscle during contraction. The results showed that this force is small compared with that developed by the diaphragm, except at very high lung volumes. It is concluded, therefore, that the mediastinum has only little influence on the mechanics of the canine diaphragm.

Development of antigen-specific T cells in mediastinal lymph nodes after intranasal immunization.

The power of cholera toxin (CT) as an effective mucosal adjuvant is well established. Because of the high toxicity of CT, its clinical use is unlikely. Therefore, the need to identify effective and non toxic mucosal adjuvants for human use is important. For this purpose, CT is largely used as a reference molecule for testing the efficacy of new candidate adjuvants in animal models. Here, we evaluated the kinetics and the localization of antigen-specific humoral and cellular immune responses elicited by intranasal immunization with tetanus toxoid antigen in the presence of CT. We show that an antigen-specific cellular immune response localized in the mediastinal lymph nodes can be observed already 1 week after the first immunization. The induction of an appreciable titer of an antibody-specific immune response was assessed after two immunizations. Therefore, we suggest that the efficacy of new candidate mucosal adjuvants can be tested by evaluating the cellular immune response in the mediastinal lymph nodes at early stages of immunization.

Extramedullary hematopoiesis: findings on computed tomography scans of the chest in 6 patients.

OBJECTIVE: To present findings on computed tomography scans of the chest indicative of extramedullary hematopoiesis in six patients. METHODS: We retrospectively analyzed computed tomography scans of six adult patients - five males and one female - with a mean age of 36.5 years. Two radiologists independently reviewed the scans, and a consensus was reached in discrepant cases. RESULTS: The most common finding in the scans was lower paravertebral masses with heterogeneous content (four patients). The scans of two patients showed a solitary parietal and pleural mass. CONCLUSIONS: There are findings in computed tomography scans that are highly suggestive of extramedullary hematopoiesis, especially when those findings correlate with underlying blood diseases. Such findings, in most of the cases, allow physicians to dispense with histopathological confirmation.

Hematopoese extramedular: achados em tomografia computadorizada do tórax de 6 pacientes / Extramedullary hematopoiesis: findings on computed tomography scans of the chest in 6 patients

OBJETIVO: Apresentar os achados na tomografia computadorizada do tórax indicativos de hematopoese extramedular de seis pacientes. MÉTODOS: Foram estudadas, retrospectivamente, as tomografias de seis pacientes adultos-cinco homens e uma mulher-com idade média de 36,5 anos. Os exames foram analisados por dois radiologistas, de forma independente, e as decisões finais foram obtidas por consenso. RESULTADOS: O achado mais freqüente nas tomografias foi o de massas paravertebrais inferiores, de conteúdo heterogêneo (quatro pacientes). As tomografias de dois pacientes mostravam uma massa solitária parietal e pleural. CONCLUSÕES: A hematopoese extramedular apresenta aspectos na tomografia computadorizada fortemente sugestivos do diagnóstico que, quando correlacionados com a presença de doença hematológica de base, permitem, na maior parte dos casos, dispensar a comprovação histopatológica.

OBJECTIVE: To present findings on computed tomography scans of the chest indicative of extramedullary hematopoiesis in six patients. METHODS: We retrospectively analyzed computed tomography scans of six adult patients - five males and one female - with a mean age of 36.5 years. Two radiologists independently reviewed the scans, and a consensus was reached in discrepant cases. RESULTS: The most common finding in the scans was lower paravertebral masses with heterogeneous content (four patients). The scans of two patients showed a solitary parietal and pleural mass. CONCLUSIONS: There are findings in computed tomography scans that are highly suggestive of extramedullary hematopoiesis, especially when those findings correlate with underlying blood diseases. Such findings, in most of the cases, allow physicians to dispense with histopathological confirmation.

Impact of diaphragmatic contraction on the stiffness of the canine mediastinum.

To assess the coupling between a particular hemidiaphragm and the individual lungs, the left and right phrenic nerves were separately stimulated in anesthetized dogs, and the mean changes in pleural pressure over the two lungs were evaluated by measuring the changes in airway opening pressure (DeltaPao) in the two bronchial trees. Stimulation induced a fall in Pao in both lungs. However, DeltaPao in the contralateral lung was only 65% of that in the ipsilateral lung. Thus, although the canine ventral mediastinum is a delicate structure, it sustained a significant pressure gradient. The hypothesis was then considered that this gradient was allowed to develop through the stretching and stiffening of the mediastinum caused by the descent of the diaphragm, and it was tested by measuring DeltaPao in the two lungs during isolated, unilateral contraction of the inspiratory intercostal muscles. In this condition, DeltaPao in the contralateral lung was 92% of that in the ipsilateral lung. A model analysis of the respiratory system led to the estimate that mediastinal elastance was approximately 25 times greater during hemidiaphragmatic contraction than during unilateral intercostal contraction. These observations indicate that 1) a particular hemidiaphragm has an expanding action on both lungs and 2) during contraction, however, it makes the mediastinum stiffer so that the pressure transmission from the ipsilateral to the contralateral pleural cavity is reduced. These observations imply that the mediastinum may play a significant role in determining the pressure-generating ability of the diaphragm.

[Severe hypoxia during right lateral position induced by mediastinal shift].

An 87-year-old woman with osteoarthrosis of her left hip joint was scheduled for total hip arthroplasty. After induction of anesthesia the patient was put into the right lateral position for surgery. Oxygen saturation had decreased gradually and the respiratory sound of the right lung was not auscultated. Broncofiberscopic examination showed that the position of the tracheal tube was appropriate and no secretion was found. Immediately after the patient was retuned to supine, oxygenation improved and the respiratory sound of the right lung was ausculated clearly. Chest radiographs were taken in both supine and right lateral positions. The chest X-ray findings taken in the right lateral position revealed that the right lung volume was decreased remarkably due to the extreme downward-shift of the mediastinum. The operation was postponed. The right lateral chest X-ray taken during wakefulness showed that the degree of mediastinal shift was not as remarkable as during anesthesia. After 8 days, the operation was performed using the supine position. We concluded that a downward mediastinal shift induced severe right lung volume reduction in the right lateral position during anesthesia.

Mediastinal lymph node CD8alpha- DC initiate antigen presentation following intranasal coadministration of alpha-GalCer.

Our previous study revealed that alpha-galactosylceramide (alpha-GalCer) is a potent nasal vaccine adjuvant inducing both potent humoral and cellular immune responses and affording complete protection against viral infections and tumors. However, the antigen-presenting cells (APC) that are activated by NKT cells and thereby initiate the immune responses following intranasal coadministration of protein antigen and alpha-GalCer are poorly understood. We assessed here where antigen presentation occurs and which APC subset mediates the early stages of immune responses when protein antigen and alpha-GalCer are intranasally administered. We show that dendritic cells (DC), but not B cells, initiated the mucosal immune responses at mediastinal lymph nodes. Of the DC subsets, the CD8alpha-B220-CD11c+ DC subset played the most prominent role in the direct and cross-presentation of protein antigen to naive T cells and in triggering the naive T cells to differentiate into effector T cells. This might be mainly caused by a relatively larger population of CD1dhigh cells of CD8alpha-B220-CD11c+ DC subset than those of other DC subsets. These results indicate that CD8alpha-B220-CD11c+ DC is the principal subset becoming immunogenic after interaction with NKT cells and abrogating tolerance to intranasally administered protein antigen when alpha-GalCer is coadministered as a nasal vaccine adjuvant.

Platypnea-orthodeoxia syndrome after pneumonectomy relieved by mediastinal repositioning.

Platypnea-orthodeoxia is a rare syndrome characterized by hypoxemia in the upright position after pneumonectomy and relieved by recumbency. This syndrome is often a post-pneumonectomy complication due to intracardiac shunt, usually at the atrial level. We report a case after right pneumonectomy without interatrial shunt. The patient was successfully treated with a silicone prosthesis implant in the post-pneumonectomy space. We believe that correction of this clinical situation has not been previously described.

Inappropriate mediastinal baroreceptor reflex as a possible cause of sudden infant death syndrome - Is thorough burping before sleep protective?

Despite extensive research, a link between the assumed mechanisms of death and known risk factors for sudden infant death syndrome (SIDS) has not yet been established. Modifiable risk factors such as prone sleeping position, nicotine exposure and thermal stress and non-avoidable risk factors like male gender and some risky socio-economic conditions could be detected, but the etiology of SIDS remains unknown. In many SIDS cases histopathological findings suggest an involvement of vital autonomic control functions and unidentified trigger factors seem to play a role. From a hypothetical point of view, a developmental sympatheticovagal imbalance of the cardiovascular reflex control could cause a predisposition for SIDS. An assumed gastroesophageal trigger impulse is possibly developed during the first weeks of life and could lead to the infant's vagal reflex death. Air swallowed during feeding escapes through the esophagus while the infant is sleeping. The temporarily bloated esophagus exerts pressure on neighboring mediastinal baroreceptors, which is potentially misinterpreted as a rise in arterial pressure. The following cardiodepressoric baroreceptor reflex could lead to arterial hypotension, bradycardia and cardiac arrest. Sleeping in prone position may create an increased thoracic pressure on mediastinal baroreceptors, causing a more pronounced vagal reflex and an increased likelihood of SIDS. Prone position in connection with soft objects in the infant's sleeping environment potentially generates an increased oculobulbar pressure, resulting in an additional cardiodepressoric condition (Aschner-Dagnini phenomenon). From the sixth month of life onwards the sympatheticovagal balance seems to have matured sufficiently to compensate the life-threatening challenges in most infants. Insufficient postprandial burping could either create another independent modifiable risk factor or present the missing link to a common trigger mechanism for SIDS. Further investigations may possibly lead to the explicit recommendation to burp all infants sufficiently and repeatedly before sleep.