Athymic nude rat. III natural cell mediated cytotoxicity.

Homozygous rnu/rnu and heterozygous +/rnu rats were investigated and compared with each other for the existence of natural cell-mediated cytotoxicity. Investigated were total, adherent, and nonadherent cell populations from spleen, peritoneal cavity, and mesenteric lymph node. The natural killer (NK) cell activity was measured in a 4-hr 51Cr-release assay with a xenogeneic murine YAC lymphoma target cell line. In both and +/rnu rats the peritoneal cavity had the highest percentage of activity, while the spleen and mesenteric lymph node showed a lower activity. The mesenteric lymph node of +/rnu rats of 8–10 weeks of age was found to express a very low activity, in contrast to a very high activity in rats. For almost every effector to target cell (E:T) ratio investigated (100, 70, 50, and 10), the natural killer cell activity in the nude rats was found to be significantly higher than in their thymus-bearing littermates. In comparison with that of +/rnu rats, NK activity in the nonadherent cell fractions of athymic rats was 50 to 60% higher in spleen cells, doubled in peritoneal cells, and increased 10-fold or higher in lymph node cells. Investigations o

Disabling Wake Up Stroke without Lesions on Initial Diffusion Weighted Imaging - Case Report and Clinical Implications

An 86-year-old lady presented after waking up with left sided paresis and neglect. Right hemispheral stroke was suspected, but initial MRI with Diffusion Weighted Imaging (DWI) was negative and there was no large vessel occlusion. We accordingly withheld intravenous thrombolysis. She did not improve clinically and follow-up MRI after three days showed a marked lesion compatible with acute ischemic stroke in the right middle cerebral artery territory. This case shows that even with a disabling stroke in the anterior circulation initial DWI may be negative. Former studies established that thrombolysis can be safe in these cases when there is no doubt about the clinical diagnosis of acute ischemic stroke

DISCOVER: Dutch Iliac Stent trial: COVERed balloon-expandable versus uncovered balloon-expandable stents in the common iliac artery: Study protocol for a randomized controlled trial

Background: Iliac artery atherosclerotic disease may cause intermittent claudication and critical limb ischemia. It can lead to serious complications such as infection, amputation and even death. Revascularization relieves symptoms and prevents these complications. Historically, open surgical repair, in the form of endarterectomy or bypass, was used. Over the last decade, endovascular repair has become the first choice of treatment for iliac arterial occlusive disease. No definitive consensus has emerged about the best endovascular strategy and which type of stent, if any, to use. However, in more advanced disease, that is, long or multiple stenoses or occlusions, literature is most supportive of primary stenting with a balloon-expandable stent in the common iliac artery (Jongkind V et al., J Vasc Surg 52:1376-1383,2010). Recently, a PTFE-covered balloon-expandable stent (Advanta V12, Atrium Medical Inc., Hudson, NH, USA) has been introduced for the iliac artery. Covering stents with PTFE has been shown to lead to less neo-intimal hyperplasia and this might lower restenosis rates (Dolmatch B et al. J Vasc Interv Radiol 18:527-534,2007, Marin ML et al. J Vasc Interv Radiol 7:651-656,1996, Virmani R et al. J Vasc Interv Radiol 10:445-456,1999). However, only one RCT, of mediocre quality has been published on this stent in the common iliac artery (Mwipatayi BP et al. J Vasc Surg 54:1561-1570,2011, Bekken JA et al. J Vasc Surg 55:1545-1546,2012). Our hypothesis is that covered balloon-expandable stents lead to better results when compared to uncovered balloon-expandable stents.Methods/Design: This is a prospective, randomized, controlled, double-blind, multi-center trial. The study population consists of human volunteers aged over 18 years, with symptomatic advanced atherosclerotic disease of the common iliac artery, defined as stenoses longer than 3 cm and occlusions. A total of 174 patients will be included.The control group will undergo endovascular dilatation or revascularization of the common iliac artery, followed by placement of one or more uncovered balloon-expandable stents. The study group will undergo the same treatment, however one or more PTFE-covered balloon-expandable stents will be placed. When necessary, the aorta, external iliac artery, common femoral artery, superficial femoral artery and deep femoral artery will be treated, using the standard treatment.The primary endpoint is absence of binary restenosis rate. Secondary endpoints are reocclusion rate, target-lesion revascularization rate, clinical success, procedural success, hemodynamic success, major amputation rate, complication rate and mortality rate. Main study parameters are age, gender, relevant co-morbidity, and several patient, disease and procedure-related parameters. Trial registration: Dutch Trial Register, NTR3381

A molecular signature of epithelial host defense: comparative gene expression analysis of cultured bronchial epithelial cells and keratinocytes

BACKGROUND: Epithelia are barrier-forming tissues that protect the organism against external noxious stimuli. Despite the similarity in function of epithelia, only few common protective mechanisms that are employed by these tissues have been systematically studied. Comparative analysis of genome-wide expression profiles generated by means of Serial Analysis of Gene Expression (SAGE) is a powerful approach to yield further insight into epithelial host defense mechanisms. We performed an extensive comparative analysis of previously published SAGE data sets of two types of epithelial cells, namely bronchial epithelial cells and keratinocytes, in which the response to pro-inflammatory cytokines was assessed. These data sets were used to elucidate a common denominator in epithelial host defense. RESULTS: Bronchial epithelial cells and keratinocytes were found to have a high degree of overlap in gene expression. Using an in silico approach, an epithelial-specific molecular signature of gene expression was identified in bronchial epithelial cells and keratinocytes comprising of family members of keratins, small proline-rich proteins and proteinase inhibitors. Whereas some of the identified genes were known to be involved in inflammation, the majority of the signature represented genes that were previously not associated with host defense. Using polymerase chain reaction, presence of expression of selected tissue-specific genes was validated. CONCLUSION: Our comparative analysis of gene transcription reveals that bronchial epithelial cells and keratinocytes both express a subset of genes that is likely to be essential in epithelial barrier formation in these cell types. The expression of these genes is specific for bronchial epithelial cells and keratinocytes and is not seen in non-epithelial cells. We show that bronchial epithelial cells, similar to keratinocytes, express components that are able to form a cross-linked protein envelope that may contribute to an effective barrier against noxious stimuli and pathogens

Granulomatous skin lesions complicating Varicella infection in a patient with Rothmund-Thomson syndrome and immune deficiency: case report

Rothmund-Thomson syndrome (RTS)(OMIM 268400) is a rare autosomal recessive genodermatosis characterized by poikiloderma, small stature, skeletal and dental abnormalities, cataract and an increased risk of cancer. It is caused by mutations in RECQL4 at 8q24. Immune deficiency is not described as a classical feature of the disease. Here we report the appearance of granulomatous skin lesions complicating primary Varicella Zoster Virus infection in a toddler with Rothmund Thomson syndrome and immune deficiency. Although granulomatous disorders are sometimes seen after Herpes zoster, they are even more rare after Varicella primary infection. Granulomas have hitherto not been described in Rothmund-Thomson syndrome. With this report we aim to stress the importance of screening for immune deficiency in patients with Rothmund-Thomson syndrome

Rotavirus vaccine response correlates with the infant gut microbiota composition in Pakistan

Rotavirus (RV) is the leading cause of diarrhea-related death in children worldwide and ninety-five percent of rotavirus deaths occur in Africa and Asia. Rotavirus vaccines (RVV) can dramatically reduce RV deaths, but have low efficacy in low-income settings where they are most needed. The intestinal microbiome may contribute to this decreased RVV efficacy. This pilot study hypothesizes that infants' intestinal microbiota composition correlates with RVV immune responses and that RVV responders have different gut microbiota as compared to non-responders. We conducted a nested, matched case-control study comparing the pre-vaccination intestinal microbiota composition between 10 6-week old Pakistani RVV-responders, 10 6-week old Pakistani RVV non-responders, and 10 healthy Dutch infants. RVV response was defined as an Immunoglobulin A of >= 20 IU/mL following Rotarix (TM)(RV1) vaccination in an infant with aprevaccination IgA RV1 response correlated with a higher relative abundance of bacteria belonging to Clostridium cluster XI and Proteobacteria, including bacteria related to Serratia and Escherichia coli. Remarkably, abundance of these Proteobacteria was also significantly higher in Dutch infants when compared to RV1-non-responders in Pakistan. This small but carefully matched study showed the intestinal microbiota composition to correlate with RV1 seroconversion in Pakistan infants, identifying signatures shared with healthy Dutch infants.Peer reviewe

Microarray and morphological analysis of early postnatal CRB2 mutant retinas on a pure C57BL/6J genetic background

In humans, the Crumbs homologue-1 (CRB1) gene is mutated in progressive types of autosomal recessive retinitis pigmentosa and Leber congenital amaurosis. Th