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.     

Hypoplastic left heart syndrome with anomalous origin of left coronary artery from the right pulmonary artery: successful surgical treatment in a neonate.

Anomalous origin of the left coronary artery from the right pulmonary artery in association with hypoplastic left heart syndrome is a rare congenital anomaly. We describe a successful simultaneous surgery for both anomalies during the first stage palliation in a neonate.     

Mammalian nuclear transfer.

During development, the genetic content of each cell remains, with a few exceptions, identical to that of the zygote. Differentiated cells, therefore, retain all the genetic information necessary to generate an entire organism (nuclear totipotency). Nuclear transfer (NT) was initially developed to test experimentally this concept by cloning animals from differentiated cells. It has, since then, been used to study the role of genetic and epigenetic alterations during development and disease. In this review, we highlight some of the milestones in mammalian NT reached in the 50 years after the first nuclear transplantations in frogs. We also address problems associated with mammalian nuclear transfer and provide a survey on current NT and stem cell technology. In the long term, nuclear transfer or alternative strategies aim to generate customized pluripotent cells, which would be invaluable to medical research and therapy.     

Abnormalities of somatosensory evoked potentials in the quinolinic acid model of Huntington's disease: evidence that basal ganglia modulate sensory cortical input.

Intrastriatal injection of quinolinic acid (QA) in rats provides an animal model that mimics some of the neuropathological and neurochemical alterations observed in the striatum of patients with Huntington's disease (HD). One of the very early neurophysiological signs in HD is a diminution of amplitude of early somatosensory evoked potentials (SEPs) recorded over the parietal cortex. The present study investigated whether the QA model exhibits similar neurophysiological abnormalities. Two weeks after unilateral intrastriatal injection of QA (240 nmol) or of the solvent, early SEPs were recorded with chronically implanted electrodes from the somatosensory cortex or from the ventrobasal nucleus of the thalamus of lightly pentobarbital-anesthetized rats, in response to single-shock electrical stimulation of the contralateral forepaw. Whereas intrastriatal injection of solvent did not influence SEPs, the striatal QA lesion significantly reduced the amplitude of early cortical SEPs by about 40% without affecting the latency. SEPs recorded from the ventrobasal nucleus were unchanged after QA lesion. Histological examination and glial fibrillary acid protein staining after intrastriatal injection of QA revealed no evidence for damage in the somatosensory system. It is concluded that (1) the QA animal model of HD mimics some of the SEP abnormalities of patients, and (2) a striatal lesion modulates somatosensory transmission to the cortex in rats.     

A promising technique for transplantation of bone marrow-derived endothelial progenitor cells into rat heart.

OBJECTIVE: To investigate the feasibility of intracoronary application of endothelial progenitor cells and the subsequent distribution within the heart. METHODS: Endothelial progenitors cells (EPCs) cultured from rat bone marrow were identified by double-positive staining with Dil-Ac-LDL and BS1-lectin. Twenty-four hours before cell transplantation, EPCs were labeled with 5-bromo-2'-deoxyuridine (BrdU). Cells (5 x 10(5) in 250-microl medium) were injected into healthy rats, either as intracoronary application (n=11) or as intramyocardial injection (n = 6). At 15 min or 3 days posttransplantation, hearts as well as other organs (lung, liver, kidney, and spleen) were collected and processed for subsequent BrdU immunohistochemistry. The number of BrdU-positive cells per tissue area was counted. RESULTS: Compared to intramyocardial injection, intracoronary administration resulted in more than twice as much positive cells in the heart (P < .05), with no local differences within the heart. Whereas after 15 min, EPCs were equally distributed in all examined organs (except for the spleen), cells that were still present after 3 days, approximately 10%, were selectively restricted to the heart. CONCLUSIONS: Our data indicate that the intracoronary application provides a promising technique for EPC transplantation in the rat heart.     

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Activation of influenza A viruses by trypsin treatment.

A comparative analysis has been carried out on the infectivity of virus of several influenza A strains grown in different host systems. Strains A/swine/Shope/31 (Hsw1N1), A/PR/8/34 (HON1), A/FM/1 (H1N1), A/Singapore/1/57 (H2N2), A/equine/Miami/1/63 (Heq2Neq2), and A/chick/Germany/49 (Hav2Neq1) exhibit host-dependent differences in infectivity. Virions grown in embryonated eggs and cultures of chorioallantoic membrane cells are highly infectious, whereas virions grown in cultures of chick embryo cells have a low infectivity that significantly increases after treatment in vitro with trypsin. In contrast, fowl plague viruses do not show host-dependent variations in infectivity. Virions grown in all host systems tested are highly infectious, and the infectivity of virions grown in chick embryo cells cannot be enhanced by trypsin treatment.The activation of virus particles appears to be based on the cleavage of hemagglutinin glycoprotein HA. This concept is supported by the following observations: (i) In virions of low infectivity only uncleaved glycoprotein HA can be detected. Virions of high infectivity exhibit complete or at least partial cleavage of the hemagglutinin. (ii) The activation of virions by trypsin treatment is always paralleled by cleavage of HA. (iii) Cleavage of HA is the only effect which can be detected after trypsin treatment. The neuraminidase is neither inactivated nor removed from the virion. (iv) Studies on recombinants of virus N and fowl plague virus (Rostock) show that host-dependent variation of infectivity and activation by trypsin, features specific for parent virus N, are found only with recombinant N(H)-FPV/Ro(N) but not with recombinant FPV/Ro(H)-N(N).Efficient plaque formation and serial passages are possible only if highly infectious particles are formed in a given host system. Thus, all strains analyzed undergo, in the absence of trypsin, successive growth cycles in eggs and chorioallantoic membrane cells and form plaques in chorioallantoic membrane cells. In contrast, in chick embryo cells only viruses containing the fowl plague virus hemagglutinin produce plaques and replicate under multiple cycle conditions without the addition of trypsin.The data show that cleavage of HA is not a precondition for virus assembly and hemagglutinating activity, but that it is necessary for infectivity. These findings are compatible with the hypothesis that, in addition to its role in adsorption, the hemagglutinin has another function in the infection process and cleavage is required for this function.     

September 2002: 24-year-old female with a 6-month history of seizures

The September 2002 COM. A 24-year-old female presented with a history of 3 generalized seizures, the first of which had occurred 6 months before admission. Her neurological examination was normal, but upon admission her MRI showed a small cystic lesion in the left parieto-occipital region. The lesion was hyper-intense on T-2 weighted images and did not show contrast enhancment. At surgery, the tumor was found to be deep to the cortex and was a cyst with amber fluid surrounded by gliotic brain. Microscopically, the tumor was well-demarcated from the surrounding tissues, which showed reactive changes, including Rosenthal fibers. The tumor was composed of GFAP-positive glial cells, which were arranged in a pseudopapillary fashion around blood vessels. In between, the tumor cells were positive for neuronal markers. The diagnosis was papillary glioneuronal tumor (PGNT), a relatively recently described lesion that may be a variant of ganglioglioma. The current literature on PGNTs is reviewed.