Early pathological changes in progressive multifocal leukoencephalopathy: a report of two asymptomatic cases occurring prior to the AIDS epidemic

Serial sections of formalin-fixed, paraffinembedded blocks from two asymptomatic, non-AIDS cases of progressive multifocal leukoencephalopathy (PML) were stained with a double-label immunocytochemical method for detection of glial fibrillary acidic protein and JC virus (JCV) capsid proteins and with luxol fast blue/hematoxylin-eosin. In case 1 small, rounded lesions of about 1-mm diameter were seen within a restricted area in the posterior part of the superior frontal gyrus of both cerebral hemispheres, suggesting an early manifestation of the disease. Fully developed demyelinated lesions of the classical type with JCV-infected oligodendrocytes appeared in the white matter and along its border with the cortex. Lesswell-developed lesions, believed to be precursors to the fully developed ones, were seen in the gray and white matter. Of special interest were areas which contained small collections of enlarged, glial fibrillary acidic protein (GFAP)-positive astrocytes without capsid antigen and which seemed to lack destruction of myelin as judged from the appearance of matching serial sections stained for myelin. Large lesions in the brain of case 2 showed the well-known features of advanced PML. The close relation between some astrocytes and oligodendrocytes with viral antigen raises the possibility of early intercellular passage of virus. Vacuolation, seen within or near lesions in both cases, has previously been noted in the CNS infected by HIV, but not in PML. It is suggested that PML, a disease of both oligodendrocytes and astrocytes, may actually begin in astroglial cells which, under the influence of a restricted JCV infection, become reactive, express GFAP and pass on virus to the more highly susceptible oligodendrocytes with which they are in contact.Supported in part by a grant N.S.07596 from the National Institute of Neurological Disorders and Stroke. The work was carried out in the Laboratory of Experimental Neurophathology, NINDS, and in the Department of Pathology II, Karolinska Institute, Stockholm     

Impact of gastrointestinal endoscopy on HIV‐infected children

Objective: To evaluate the role of gastrointestinal (GI) endoscopy in human immunodeficiency virus (HIV)‐infected children with GI problems. Methods: From 1998 to 2002, we retrospectively reviewed all cases of HIV‐infected children presenting with GI problems in which an upper or lower GI endoscopy was indicated. The initial diagnostic endoscopic examination and any repeat endoscopic session leading to a new diagnosis were used in the data analysis. Tissue biopsies were obtained from all abnormal lesions and representative sites of normal‐appearancing GI mucosa. Results: Fourteen patients (median age: 22.5 months) underwent 23 sessions of GI endoscopy, including 10 esophagogastroduodenoscopy, nine colonoscopy and four flexible sigmoidoscopy. Chronic diarrhea was the most common indication, followed by lower GI bleeding, abdominal/retrosternal pain, dysphagia/odynophagia, and upper GI bleeding. Gross endoscopic abnormalities were observed in 78.3%; whereas histological inflammation and opportunistic pathogens were identified in 87% and 43.5%, respectively. Cytomegalovirus was the most common identified pathogen. Abnormal gross findings were significantly associated with histological inflammation and identification of pathogens (P = 0.006 and 0.046, respectively). Specific changes in medical management were made in 50% of cases as a result of endoscopic investigation. Conclusion: If non‐invasive investigations for HIV‐infected children with GI symptoms fail to establish a diagnosis, gastrointestinal endoscopy should be performed and often yields a positive result leading to changes in medical management.     

Clinical Impact of Community-Acquired Respiratory Viruses on Bronchiolitis Obliterans After Lung Transplant

Community-acquired viral respiratory tract infections (RTI) in lung transplant recipients may have a high rate of progression to pneumonia and can be a trigger for immunologically mediated detrimental effects on lung function. A cohort of 100 patients was enrolled from 2001 to 2003 in which 50 patients had clinically diagnosed viral RTI and 50 were asymptomatic. All patients had nasopharyngeal and throat swabs taken for respiratory virus antigen detection, culture and RT-PCR. All patients had pulmonary function tests at regular intervals for 12 months. Rates of rejection, decline in forced expiratory volume (L) in 1 s (FEV-1) and bacterial and fungal superinfection were compared at the 3-month primary endpoint. In the 50 patients with RTI, a microbial etiology was identified in 33 of 50 (66%) and included rhinovirus (9), coronavirus (8), RSV (6), influenza A (5), parainfluenza (4) and human metapneumovirus (1). During the 3-month primary endpoint, 8 of 50 (16%) RTI patients had acute rejection versus 0 of 50 non-RTI patients (p=0.006). The number of patients experiencing a 20% or more decline in FEV-1 by 3 months was 9 of 50 (18%) RTI versus 0 of 50 non-RTI (0%) (p=0.003). In six of these nine patients, the decline in FEV-1 was sustained over a 1-year period consistent with bronchiolitis obliterans syndrome (BOS). Community-acquired respiratory viruses may be associated with the development of acute rejection and BOS.     

Mapping the rat somatosensory pathway from the anterior cruciate ligament nerve endings to the cerebrum

The anterior cruciate ligament (ACL) serves as the primary restraint to anterior tibial translation. In addition to this biomechanical function, the ACL appears to have a function in neuromuscular control. This hypothesis was formulated after the discovery of mechanoreceptors within the ACL. The full somatosensory pathway from the ACL to the cerebrum has yet to be elucidated. In order to map this sensory pathway, we conducted a viral trans-synaptic tracing experiment using the neurotropic pseudorabies virus (PRV). The pseudorabies virus was injected into the ACL of rats and allowed to replicate and spread trans-synaptically for 6-7 days. The brain and spinal cord of each sacrificed rat was then removed and processed immunohistochemically to detect the presence of PRV. PRV-immunoreactive neurons were found to be localized in several different regions from the spinal cord to the cerebrum. Four nuclei in the reticular formation of the brain stem demonstrated strong positive labeling: the mesencephalic reticular nucleus, magnocellular reticular nucleus, paragigantocellular reticular nucleus, and gigantocellular reticular nucleus. This finding suggests that the nerve endings of the rat ACL project into the cerebrum and that the reticular formation may play an important role in the afferent pathway of those nerve endings.     

Human Herpesvirus 6 in Bronchalveolar Lavage Fluid after Lung Transplantation: A Risk Factor for Bronchiolitis Obliterans Syndrome?

Bronchiolitis obliterans syndrome (BOS) is the limiting factor to long-term survival after lung transplantation. Previous studies suggested respiratory viral tract infections are associated with the development of BOS. To identify the impact of virus detection in bronchoalveolar lavage (BAL) fluid, we analyzed BAL samples from 87 consecutive lung transplant recipients for human herpesvirus (HHV)-6, Epstein-Barr virus, Herpes simplex virus 1/2, Cytomegalovirus, respiratory syncytical virus and adenovirus by PCR. Acute rejection, BOS and death were recorded for a mean follow-up time of 3.27 +/- 0.47 years. Results of PCR analysis and other potential risk factors were entered into a Cox regression analysis of BOS predictors and death. Only acute rejection was a distinct risk factor for BOS of all stages, death and death from BOS. HHV-6 was detected in 20 patients. Univariate and multivariate analysis revealed that HHV-6 was associated with an increased risk to develop BOS > orb = stage 1 and death, separate from the risk attributable to acute rejection. Identification of HHV-6 DNA in BAL fluid is a potential risk factor for BOS. Our results warrant further studies to elucidate a possible causal link between HHV-6 and BOS.     

医院用血液制品HCV污染情况的调查

目的调查医院治疗用血液制品ＨＣＶ污染情况．方法临床治疗所用的血液制品，在输完后留容器之残液备检．采用酶标免疫法（ＥＬＩＳＡ）检测．对ＥＬＩＳＡ检测之阳性标本及在阴性标本中随机抽取９份，采用逆转录双ＰＣＲ方法检测ＨＣＶ＿ＲＮＡ．结果血浆白蛋白抗＿ＨＣＶ阳性率４５８％，新鲜血浆阳性率２６％．两种方法检测同一标本，ＥＬＩＳＡ检测阳性的血液制品中，用ＰＣＲ证实，并非都有病毒复制；而在ＥＬＩＳＡ检测的阴性标本中，仍旧有较高的ＰＣＲ阳性检出．结论血液制品存在着ＨＣＶ污染，抗＿ＨＣＶ对于ＨＣＶ感染的诊断价值很高．检测血液制品中的抗＿ＨＣＶ，合理使用血液成份，可防止ＨＣＶ在医院内传播．     

PCR检测角膜内单疱病毒DNA的实验及临床研究

为了探索单疱病毒性角膜炎的发病机制和快速诊断ＨＳＫ。方法应用多聚酶链反应对感染的ＨＳＫ的２０只纯新西兰白兔和６０例ＨＳＫ患者的角膜进行了单疱病毒－１－ＤＮＡ检测。结果急性感染期的５只兔角膜和１２只人角膜均阳性；用稳定期４５ｄ的兔角供体行部分穿透性角膜移植术，术后５０ｄ１０只兔角膜中７只阳性，稳定期６个月－６年的１８只人角膜片，１２只阳性；３０例临床可疑ＨＳＫ角膜刮取物，２６例阳性；５只未感染ＨＳＫ     

Periodontal diseases in HIV-infected patients

Abstract Periodontal diseases may be the first clinical sign of human immunodeficiency virus (HIV)-infection. Since the immunosuppression and subsequent susceptibility may alter the responses of the oral tissues as well as the microflora, both periodontal treatment and result of therapy may be modified. The periodontal diseases in HIV-seropositive patients include common as well as less conventional forms of gingivitis and periodontitis, and bacteria, mycotic and viral infections are seen. Neoplasias may also involve the periodontium; most common are Kaposi's sarcoma and non-Hodgkin's lymphoma. Recent studies of unselected groups of patients indicate that periodontal health in at least some groups of HIV-seropositive patients is better than previously reported.     

Antibodies against dengue virus E protein peptide bind to human plasminogen and inhibit plasmin activity

Both mice and rabbits immunized with dengue virus E protein peptide spanning amino acids 100–119 (D4E) produced antibodies that reacted not only with the D4E peptide itself but also with human plasminogen, as shown by ELISA and Western blot. Sera from dengue virus-hyperimmunized mice and dengue patients also contained antibodies against D4E and plasminogen. Furthermore, such sera all contained plasmin inhibitory activity. Using affinity-purified anti-D4E antibodies and free D4E peptide for competitive inhibition, we demonstrated that the inhibition of plasmin activity was due to anti-D4E antibodies rather than other substances in the sera. Taken together, these results suggest dengue virus E protein amino acids 100–119 are a cross-reactive immunogenic region, and antibodies against this region may interfere with human fibrinolysis.     

Varicella in a gorilla

Naturally occurring varicella was observed in a young gorilla in captivity. The isolate was demonstrated to be varicella-zoster virus by restriction enzyme analysis.