The influence of HLA A-B-DR matching on cytomegalovirus disease after renal transplantation. Evidence that HLA-DR7-matched recipients are more susceptible to cytomegalovirus disease.

We examined the prevalence of cytomegalovirus infectious episodes, as defined by clinical, virological, and serological criteria (i.e., CMV disease), in 660 kidney graft recipients; 109 patients (16.5%) developed the disease, and 551 did not. No significant statistical link between CMV disease prevalence and a given HLA-A, -B, or -DR allele was observed. However, patients with HLA-DR7 matched grafts were statistically more frequently found (P < 0.01) in the group of recipients who developed CMV disease as compared with the group who did not develop CMV disease. Furthermore, among patients who developed CMV disease, a significant increase of HLA-DR7 matched over DR7 mismatched patients was noted, whereas no difference between matched and mismatched recipients for the other HLA-DR alleles was found. No difference in the severity of graft failure, often observed during, or immediately after, the CMV episode, was noted between patients matched or mismatched for HLA-DR7. Our data suggest that donor/recipient matching for HLA-DR7 is associated with increased CMV disease.     

What is the place of electroneuromyographic studies in the diagnosis and management of pudendal neuralgia related to entrapment syndrome?

Entrapment of the pudendal nerve may be at the origin of chronic perineal pain. This syndrome must be diagnosed because this can result in the indication of surgical decompression of the entrapped nerve for pain relief. Electroneuromyographic (ENMG) investigation is often performed in this context, based on needle electromyography and the study of sacral reflex and pudendal nerve motor latencies. The limits of ENMG investigation, owing to various pathophysiological and technical considerations, should be known. The employed techniques do not assess directly the pathophysiological mechanisms of pain but rather correlate to structural alterations of the pudendal nerve (demyelination or axonal loss). In addition, only direct or reflex motor innervation is investigated, whereas sensory nerve conduction studies should be more sensitive to detect nerve compression. Finally, ENMG cannot differentiate entrapment from other causes of pudendal nerve lesion (stretch induced by surgical procedures, obstetrical damage, chronic constipation...). Thus, perineal ENMG has a limited sensitivity and specificity in the diagnosis of pudendal nerve entrapment syndrome and does not give direct information about pain mechanisms. Pudendal neuralgia related to nerve entrapment is mainly suspected on specific clinical features and perineal ENMG examination provides additional, but no definitive clues, for the diagnosis or the localization of the site of compression. In fact, the main value of ENMG is to assess objectively pudendal motor innervation when a surgical decompression is considered. Perineal ENMG might predict the outcome of surgery but is of no value for intraoperative monitoring.     

Identification and characterization of a rat protein (p 105) auto-antigenic in rats bearing a progressive syngeneic colon carcinoma.

Sera from BDIX rats inoculated with 2 tumor clones derived from a single syngeneic colon carcinoma were assayed by Western blotting for the presence of antibodies against the grafted tumor. The PROb clone is progressive and produces metastases. We observed that rats bearing this tumor developed antibodies against an unglycosylated water-soluble protein of 105 kDa. The magnitude of this humoral response, as assessed by the intensity of the signal on immunoblots, was inversely correlated with survival of the rats. Furthermore, rats inoculated with the REGb clone, which is immunologically rejected, never developed detectable antibodies against the tumor. Antisera from rats injected with PROb tumor detected p105 antigen in cellular extracts from the REGb clone and from a series of rat and human cell lines. This protein was also detected in variable amounts in some normal adult and fetal tissues. Treatment of PROb or REGb cells by either interferon-gamma or heat shock did not significantly alter the expression of the p105 auto-antigen.     

Spontaneous resolution of prenatally diagnosed dural sinus thrombosis: a case report.

Fetal thrombosis of the dural sinus is an extremely rare congenital cerebrovascular condition that is potentially fatal. We report a case of dural sinus thrombosis diagnosed by prenatal ultrasonography and fetal magnetic resonance imaging (MRI) in the second trimester. The thrombosis showed partial resolution during pregnancy and resolved spontaneously after birth without neurological complications. This is the first report of spontaneous postnatal resolution, and may provide helpful information on the natural history and prenatal counseling of fetal thrombosis of the dural sinus.     

Pulmonary pathological features in coronavirus associated severe acute respiratory syndrome (SARS)

BACKGROUND: Severe acute respiratory syndrome (SARS) became a worldwide outbreak with a mortality of 9.2%. This new human emergent infectious disease is dominated by severe lower respiratory illness and is aetiologically linked to a new coronavirus (SARS-CoV). METHODS: Pulmonary pathology and clinical correlates were investigated in seven patients who died of SARS in whom there was a strong epidemiological link. Investigations include a review of clinical features, morphological assessment, histochemical and immunohistochemical stainings, ultrastructural study, and virological investigations in postmortem tissue. RESULTS: Positive viral culture for coronavirus was detected in most premortem nasopharyngeal aspirate specimens (five of six) and postmortem lung tissues (two of seven). Viral particles, consistent with coronavirus, could be detected in lung pneumocytes in most of the patients. These features suggested that pneumocytes are probably the primary target of infection. The pathological features were dominated by diffuse alveolar damage, with the presence of multinucleated pneumocytes. Fibrogranulation tissue proliferation in small airways and airspaces (bronchiolitis obliterans organising pneumonia-like lesions) in subpleural locations was also seen in some patients. CONCLUSIONS: Viable SARS-CoV could be isolated from postmortem tissues. Postmortem examination allows tissue to be sampled for virological investigations and ultrastructural examination, and when coupled with the appropriate lung morphological changes, is valuable to confirm the diagnosis of SARS-CoV, particularly in clinically unapparent or suspicious but unconfirmed cases.     

CD4 lymphocytes in the blood of HIV(+) individuals migrate rapidly to lymph nodes and bone marrow: support for homing theory of CD4 cell depletion

Recent studies have provided evidence that macrophages from Th1-prone mouse strains respond with an M1 profile, and macrophages from Th2-prone mouse strains respond with an M2 profile, characterized by the dominant production of NO or TGF-beta 1, respectively. We have shown that peritoneal macrophages from IL-12p40 gene knockout mice have a bias toward the M2 profile, spontaneously secreting large amounts of TGF-beta 1 and responding to rIFN-gamma with weak NO production. Moreover, IL-12p40KO macrophages are more permissive to Trypanosoma cruzi replication than their wild-type littermate cells. Prolonged incubation with rIL-12 fails to reverse the M2 polarization of IL-12p40KO macrophages. However, TGF-beta 1 is directly implicated in sustaining the M2 profile because its inhibition increases NO release from IL-12p40KO macrophages. IFN-gamma deficiency is apparently not the reason for TGF-beta 1 up-regulation, because rIFN-gamma KO macrophages produce normal amounts of this cytokine. These findings raise the possibility that IL-12 has a central role in driving macrophage polarization, regulating their intrinsic ability to respond against intracellular parasites.     

Decreased anti-donor major histocompatibility complex class I and increased class II alloantibody response in allograft tolerance in adult rats

Permanent tolerance to allografts can be induced in adult rats by donor-specific transfusions (DST) prior to transplantation. We have previously reported, in a model of heart allograft, the presence of a heavy leukocyte infiltrate, in the allograft which displayed a strong allospecific cytotoxicity when tested in vitro against donor cells, and a strong accumulation of mRNA for granzyme A and perforin in vivo. In contrast, there was a major decrease in the accumulation of mRNA for interleukin-2 and interferon-γ. These results suggested that the DST-induced tolerance was associated with a decrease in type-1 T helper (Th1) cell function. The major role of preformed antibodies in xeno and allorejection is clearly established. Nevertheless, the consequences of alloantibody production in acute rejection and tolerance induction remains to be elucidated. We here analyze the alloantibody response in rejecting and DST-treated recipients. We show that, after transplantation, tolerant recipients, in contrast to rejecting ones, mount a low IgM alloresponse that switches to low IgG production. Detailed analysis of IgG alloantibodies in DST-treated recipients revealed that their production decrease was not equally distributed. Whereas rejecting animals mounted a strong anti-class I and II IgG alloantibody response, DST-treated recipients produced anti-class II and low titers of anti-class I IgG alloantibodies. Furthermore, among IgG subclasses, tolerant recipients predominantly produced IgG2a, a profile which, in the rat, is compatible with a Th2-controlled response. Finally, the passive transfer of immune serum from rejecting animals to DST-treated recipients could abrogate the tolerance. We suggest that the absence of anti-class I alloantibodies combined with preserved and/or increased anti-class II production plays a major role in graft tolerance in this model. These results reinforced the role of alloantibodies in rejection and in induction of tolerance.