The natural killer cell activating receptor,NKG2D,is critical to antibody-dependent chronic rejection in heart transplantation

Chronic rejection is among the most pressing clinical challenges in solid organ transplantation. Interestingly, in a mouse model of heterotopic heart transplantation, antibody-dependent, natural killer (NK) cell-mediated chronic cardiac allograft vasculopathy occurs in some donor–recipient strain combinations, but not others. In this study, we sought to identify the mechanism underlying this unexplained phenomenon. Cardiac allografts from major histocompatibility complex (MHC) mismatched donors were transplanted into immune-deficient C57Bl/6.rag^−/− recipients, followed by administration of a monoclonal antibody against the donor MHC class I antigen. We found marked allograft vasculopathy in hearts from C3H donors, but near-complete protection of BALB/c allografts from injury. We found no difference in recipient NK cell phenotype or intrinsic responsiveness to activating signals between recipients of C3H versus BALB/c allografts. However, cardiac endothelial cells from C3H allografts showed an approximately twofold higher expression of Rae-1, an activating ligand of the NK cell receptor natural killer group 2D (NKG2D). Importantly, the administration of a neutralizing antibody against NKG2D abrogated the development of allograft vasculopathy in recipients of C3H allografts, even in the presence of donor-specific antibodies. Therefore, the activating NK cell receptor NKG2D is necessary in this model of chronic cardiac allograft vasculopathy, and strain-dependent expression of NK activating ligands correlates with the development of this disease.     

Targeting NF-κB c-Rel in regulatory T cells to treat corneal transplantation rejection

The relevance of Tregs in the induction of tolerance against corneal allografts has been well established. Although it is well known that the conversion of Tregs into effector-like cells contributes to the loss of corneal immune privilege, the underlying mechanism is still not fully understood. Using heterologous penetrating keratoplasty model, we found that Tregs from corneal allograft rejected mice (inflam-Tregs) exhibit impaired function and characteristics of effector T cells. Further study showed that the expression of NF-κB c-Rel, a key mediator of effector T cell function, was significantly increased in inflam-Tregs. Mechanistic study revealed that elevated NF-κB c-Rel level in inflam-Tregs impaired Treg function through the promotion of inflammatory cytokine production and glycolysis. More importantly, we demonstrated that targeting NF-κB c-Rel was able to improve the immune suppressive function of inflam-Tregs in vitro and enhance the potential of them to suppress corneal transplantation rejection. Therefore, our current study identified NF-κB c-Rel as a key mediator of the conversion of Tregs into effector-like cells when under inflammatory environment.     

Administration of ATG according to the absolute T lymphocyte count during therapy for steroid-resistant rejection

In renal transplantation, treatment of steroid-resistant rejection (SRR) with antithymocyte globulin (ATG) has been widely reported but over-immunosuppression remains a common problem. In the first ten patients (group 1) treated for SRR with rabbit ATG, three developed serious viral infections and two deaths occurred due to CMV pneumonitis. ATG was only omitted if thrombocytopenia or neutropenia occurred. In the next 17 patients (group 2) with SRR, ATG was administered according to the absolute T lymphocyte count. T lymphocytes were measured by flow cytometric analysis of CD3-labelled lymphocytes. ATG dosage was adjusted on a daily basis to keep the absolute T lymphocyte count under 50 cells/l. Administration of ATG according to the absolute T lymphocyte count resulted in a significant reduction in the mean dose of ATG given to the group 2 patients (P<0.001). A significant decrease in the incidence of serious viral infections (P=0.04) was achieved without reducing the ability of ATG to reverse the SRR (P=0.29) or increasing the number of grafts lost at 1 year in the group 2 patients (P=0.23).     

Binding and specificity of major immunoglobulin classes of preformed human anti-pig heart antibodies

Preformed human anti-pig antibodies isolated from perfused pig hearts were used to analyze the binding of various immunoglobulin classes to cultured pig kidney cells. All anti-pig immunoglobulins (i.e., IgG, IgA, and IgM) were localized on the cell surface by the use of an indirect immunofluorescence technique. Anti-pig immunoglobulins also competed for the pig cell surface epitopes with Griffonia simplicifolia lectin (GS-I-B₄), which is specific for -galactosyl residues. This study provides further evidence that preformed human antibodies recognizing -glactosyl-containing epitopes (anti-gal antibodies) could be an important factor in hyperacute rejection of pig organs.     

移植肾慢性排斥纤维化中巨噬细胞和NO作用机制的探讨

目的：探讨移植肾慢性排斥中纤维化过程扣形成机制。方法：采用免疫化技术及图像分析技术,观察移植肾慢性斥形成过程中巨噬细胞的形态学特征及NO含量的变化。结果：移植肾慢必排斥早、中期,损害的肾小球、肾小管处巨噬细胞增多、聚集,NO表达率增加,Ⅲ、Ⅳ型胶原的表达增强;后期,已硬化的肾小班干部、肾小管处的巨噬细胞无NO表达,Ⅲ、Ⅳ型胶原的表达减弱,CD68阳性细胞计数,NO以及Ⅲ、Ⅳ型胶原的含量在移植性肾小球病型的肾小球以及肾间质硬化型的肾小管中最高。结论：移植肾慢性排斥形成过程中巨噬细胞增多且NO表达增加,可能与肾纤维化形成有关。     

豚鼠至大鼠异种小肠移植超急性排斥的初步观察

目的 建立袖套法豚鼠至大鼠异种小肠移植模型,初步观察异种小肠移植超急性排斥反应的过程。方法 行异种异位全小肠移植,移植小肠脾性系膜上动脉（腹主动脉）与受体肾以下腹主动脉作端侧吻合,切除受体左肾,移植小肠肠系膜上静脉（门静脉）与受体左肾静脉行袖套吻合;在手术显策镜下观察超急性排斥的大体变化。结果 共实施异种小肠移植４０例,成功３４例,供受体手术时间平均１５０ｍｉｎ,血管吻合成功率达９０％。再灌流后１     

Munchausen syndrome by proxy and factitious illness: Symptomatology,parent-child interaction,and psychopathology of the parents

The term Munchausen syndrome by proxy is used to diagnose children presenting symptoms of an organic disorder resulting from manipulations initiated by their caretakers. Even in early infancy it happens that injuries are induced, and that drugs, poisons or medicine are administered in order to provoke and feign clinical symptoms of severe diseases. Exact data on prevalence are not available but it is obvious that Munchausen syndrome by proxy is a rare psychiatric disorder. There is a body of evidence that Munchausen syndrome by proxy is nothing but the extreme of a broader clinical entity for which the term factitious illness has been introduced. In this group children are included whose mothers invent a history of disease in order to produce symptoms without actually damaging their children. It is not well established whether such a distinction is necessary and whether there are differences in long-term outcome. Onset of symptoms is as early as three weeks up to twelve years, and mean age of diagnosis according to a more comprehensive study is 3 1/4 year. The estimated mortality rate of children with Munchausen syndrome by proxy is 9 percent. In three of the four cases of children reported here clinical presentations were dominated by symptoms of central nervous disorders. All mothers showed unsure and inconsistent parental behaviour and inefficient coping. None of them received support from their partners, if present. In interaction the children always wanted to dominate their mothers. The high amount of personality disorders observed in the caretakers might be the reason for the often reported failure of psychotherapeutic interventions.

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Zusammenfassung Die Diagnose Münchhausen Stellvertreter Syndrom wird bei Kindern gestellt, die Symptome einer organischen Erkrankung zeigen, die durch Manipulationen von Eltern oder anderen Sorgeberechtigten hervorgerufen werden. Vielfach werden bereits im frühen Kindesalter den Kindern Verletzungen beigebracht, Drogen, Gifte oder Medikamente verabreicht, um die klinischen Merkmale schwerer Erkrankungen vorzutäuschen. Obwohl genaue Angaben zur Häufigkeit fehlen, kann man insgesamt von einer seltenen Störung ausgehen. Es gibt zahlreiche Hinweise dafür, daß es sich beim Münchhausen Stellvertreter Syndrom um die seltene, aber sehr schwere Ausprägungsform in einer größeren Gruppe von Störungen gleichartigen klinischen Bildes handelt, für die man den Begriff der vorgetäuschte Störungen geprägt hat. In dieser Gruppe werden auch die Kinder erfaßt, deren Mütter ausschließlich Symptome und eine zugehörige Krankheitsgeschichte erfinden, die aber keine körperlichen Eingriffe (einschließlich Drogen- und Medikamentenverabreichung) vornehmen, um organische Symptome zu simulieren. Unklar ist, ob eine solche Unterscheidung notwendig und hilfreich ist. Bisher fehlen Hinweise auf Unterschiede in der Prognose im Langzeitverlauf zwischen den Untergruppen. Die Symptomatik eines Münchhausen Stellvertreter Syndroms konnte bereits bei Kindern im Alter von 3 Wochen beobachtet werden und wurde noch bei 12jährigen gefunden. In einer größeren Studie wurde ein mittleres Alter von 3 3/4Jahren für den Zeitpunkt der Diagnosestellung ermittelt. Die Sterblichkeitsrate wird auf 9 Prozent geschätzt. Bei den vier Kindern, über deren Symptomatik hier berichtet wird, standen bei drei zentralnervöse Störungen im Vordergrund. Drei Mütter gaben zusätzlich den Verdacht des sexuellen Mißbrauchs ihrer Kinder an. Die motivationalen Aspekte lassen deudiche Unterschiede erkennen. Bei drei Müttern bestand der Wunsch nach Schutz des Kindes vor realem oder vermeintlichem sexuellem Mißbrauch des Kindes. Alle Mütter hatten mindestens eine gescheiterte eheliche Beziehung. Im Erziehungsverhalten wirkten sie unsicher, inkompetent und inkonsistent; von ihren Partnern, sofern vorhanden, erhielten sie keine erzieherische Unterstützung. In der Mutter-Kind Interaktion vermochten die Kinder über die Mütter zu dominieren. Der hohe Anteil an Persönlichkeitsstörungen bei den hier beschriebenen Sorgeberechtigten könnte der Grund für das häufig berichtete Scheitern psychotherapeutischer Interventionen sein.

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Résumé On parle de Syndrôme de Munchausen par procuration chez des enfants, qui présentent des troubles organiques résultant de manipulations de leurs responsables éducatifs. Des blessures, l'administration de médicaments, de drogues ou de poison — même chez des enfants très jeunes — ont pour effet de provoquer et simuler un tableau clinique sévère. Il s'agit d'un désordre psychiatrique rare — les chiffres exacts de prévalence sont difficiles à évaluer. Le Syndrome est décrit chez l'enfant à partir de l'âge de trois semaines jusqu'à 12 ans. L'âge moyen est de trois ans et quart. La mortalité chez les enfants porteurs d'un syndrome de Munchausen par procuration est estimé à 9%. Dans trois des quatre cas présentés le tableau clinique est dominé par des symptômes d'ordre neurologique. De manière supplémentaire trois mères rapportent un abus sexuel de leurs enfants. Les mères se caracterisent par leur incompétence et inconséquence éducative; souvent elles sont sans soutien éducatif de leur partenaire. Dans l'interaction mère — enfant les enfants ont un comportement dominant envers leur mère. La non-efficacité des interventions psychothérapeutiques peut être liée a un pourcentage élevé de troubles de la personnalité chez les parents.

     

The family attitudes towards febrile convulsions

Giving adequate information about febrile convulsion and its prognosis would be helpful in alleviating parental stress, and would contribute to decrease in the morbidity of febrile convulsion. In this study, the knowledge level of parents on taking body temperature, and decreasing high fever, their attitudes during febrile convulsion and the impact of febrile convulsion on parents are evaluated. One hundred seventy-four parents of 132 children with FC were enrolled in the study. Twenty-seven per cent of parents had no thermometer at home, 32.8% of them did not know how to take a temperature, 72.2% of them did not know the minimum range of increased body temperature, and 69.5% of them did not know how to decrease the increased body temperature. Thirty-six percent of parents recognised the convulsions when their children suffered from them, the others assumed the convulsion were fainting spells (6.9%), near death state (38.5%) and suffocation (18.4%). Thirty-six per cent of parents brought their children to the hospital without doing anything themselves. Most parents (91.4%) had a fear of a recurrence of febrile convulsion in their children. Seventy-four per cent of parents complained of insomia, 24.3% parents had dyspeptic symptoms even 14 parents had weight loss due to dyspepsia.     

中／长链脂肪乳注射液的临床研究

目的研究中／长链脂肪乳注射液的临床有效性和安全性。方法本研究为随机双盲、平行对照、多中心实验设计,符合研究方案、需要肠外营养的住院病人161例进入本研究。其中120例为有对照的安全性和有效性研究,另设41例观察较长时间不良反应。结果两组中／长链脂肪乳在氮平衡、前白蛋白和术后与感染有关的并发症等方面作用相似,均无明显不良反应。结论本研究的中／长链脂肪乳是安全有效的肠外营养药物。     

Pediatric intestinal transplantation

Advancements in donor management, organ preservation and operative techniques, as well as immunosuppressive therapies, have provided children with intestinal failure and its complications a chance not only for enteral autonomy but also long-term survival through intestinal transplantation (ITx). First described in the 1960’s, experience has grown in managing these complex patients both pre- and post-transplant. The goals of this review are to provide a brief history of intestinal transplantation and intestinal rehabilitation in pediatric patients, followed by focused discussions of the indications for ITx, induction and maintenance immunosuppression therapies, common post-operative complications, and outcomes/quality of life post-transplant.