Anti-soluble liver antigen (SLA) antibodies in chronic HCV infection

Hepatitis C infection is associated with autoimmune disorders, such as the production of autoantibodies. Anti-LKM1 and anti-LC1, immunomarkers of type 2 autoimmune hepatitis, have been previously associated with a HCV infection. Anti-Soluble-Liver-Antigen autoantibodies (SLA) are specifically associated with type 1 and type 2 autoimmune hepatitis and more closely related to patients who relapse after steroid therapy. The recent molecular cloning of the soluble liver antigen provides the opportunity to develop more specific tests for the detection of antibodies against it. The aim of this work is to characterize anti-soluble-liver autoantibodies in sera from patients chronically infected by HCV. A recombinant cDNA from activated Jurkat cells coding for the full length tRNP(Ser)Sec/SLA antigen was obtained. ELISA, Western Blot and immunoprecipitation tests were developed and used to search for linear and conformational epitopes recognized by anti-SLA antibodies in sera from patients chronically infected by HCV. Anti-soluble liver antigen antibodies were found in sera from 10.4% of HCV-infected patients. The prevalence was significantly increased to 27% when anti-LKM1 was also present. Most anti-SLA reactivity was directed against conformational epitopes on the antigen. The means titers by ELISA were lower than those obtained in type 2 AIH. The result of autoantibody isotyping showed a subclass restriction to IgG1 and also IgG4. This study shows the presence of anti-SLA antibodies in approximately 10% of HCV infected patients. The prevalence of SLA autoantibodies in HCV infected patients increases when LKM1 autoantibodies are also present. The relationship between the prevalence of this characteristic autoimmune hepatitis autoantibody and the implication of an autoimmune phenomenon in the liver injury of patients chronically infected by HCV needs further investigation.     

Gene-for-gene interactions of five cloned avirulence genes from Xanthomonas campestris pv. malvacearum with specific resistance genes in cotton

A total DNA clone bank of a strain of Xanthomonas campestris pv. malvacearum (Xcm) was constructed in the cosmid vector pSa747 and transfected into Escherichia coli. The Xcm strain carries at least nine identifiable avirulence (A) genes. Clones in E. coli were mated individually into a recombination-proficient Xcm isolate carrying no known A genes. Screening was for incompatibility on congenic cotton host lines that differ by single specific resistance (R) genes. Ten different cosmid clones conferring race-specific avirulence were recovered. In most cases, the same A gene clone was recovered independently several times. Using the congenic host lines and the merodiploid transconjugant pathogen strains, five of the A genes were shown to specifically interact, gene-for-gene, with individual R genes in the congenic cotton lines. Some A/R gene interactions appeared qualitatively different from others, suggesting that the physiological mechanism(s) of gene-for-gene specified incompatibility may be unique to the interactive gene pair. All A genes appeared to be chromosomally determined, three were found linked on a single 32-kilobase clone, and the rest were spaced more than 31 kilobases apart. Colinearity of the cosmid inserts with the Xcm recipient (carrying no known A genes) chromosome was demonstrated in two of the three tested. This and other evidence suggests that at least some A genes in bacteria may have the equivalent of virulence (a) alleles. The genetics of race specificity in this phytopathogenic bacterium appeared in all respects to be identical to that found in phytopathogenic fungi.     

Pharmacokinetics and tissue disposition of the biological response modifier BAY i 7433 (copovithane) in patients with cancer

Summary Copovithane is an uncharged, water-soluble, synthetic polymer with an average molecular weight of 5800 daltons. It demonstrates antitumor activity in vivo against a variety of tumors in animal models but is inactive in vitro. This agent has been found to have immunorestorative activity in man. In concert with its phase I clinical trial, copovithane concentrations were analyzed by HPLC in plasma, urine, and autopsy and in tumor biopsy specimens obtained from patients. Copovithane was cleared from plasma biphasically with a mean t_1/2 of 11.1±4 min and a t_1/2 of 246±78 min at the dose of 1 g/m², while the plasma half-lives increased to 57.7±12 and 718±149 for the alpha and beta phases, respectively, at the 10 g/m² dose, demonstrating clear, dose-dependent pharmacokinetics. There were no significant differences between dose 1 and dose 4 pharmacokinetics. The apparent volume of distribution (V_d) was 14.5±1. at the 1 g/m² dose and increased to 73 1. at the 33 g/m² dose. The calculated mean clearance rate for copovithane in plasma was between 2.4 and 5.4 mg/kg x min and did not appear to be dose-dependent. The urinary excretion of copovithane was approximately 5% of the administered dose over 120 h at the 1 g/m² dose and decreased to 1% at the 33 g/m² dose. In seven tumor biopsy samples, concentrations of drug in tumor varied from 1- to 1000-fold higher than that found in concurrent plasma samples. In three autopsy samples, the highest concentrations were found in kidney, intestine, and liver, in decreasing order. These studies show that copovithane exhibits dose-dependent changes in pharmacokinetics at doses between 1 and 33 g/m². However, copovithane does penetrate well to tumor tissues, achieving high tumor/plasma ratios. In addition, copovithane concentrations were highest in kidney tissue, which may be a site for potential organ toxicity.     

Combined Effects of Exercise and Phytoanabolic Extracts in Castrated Male and Female Mice

Dry extracts from the Eurasian plants, Ajuga turkestanica, Eurycoma longifolia, and Urtica dioica have been used as anabolic supplements, despite the limited scientific data on these effects. To assess their actions on early sarcopenia signs, male and female castrated mice were supplemented with lyophilized extracts of the three plants, isolated or in association (named TLU), and submitted to resistance exercise. Ovariectomy (OVX) led to body weight increase and non-high-density cholesterol (HDL) cholesterol elevation, which had been restored by exercise plus U. dioica extract, or by exercise and TLU, respectively. Orchiectomy (ORX) caused skeletal muscle weight loss, accompanied by increased adiposity, being the latter parameter reduced by exercise plus E. longifolia or U. dioica extracts. General physical activity was improved by exercise plus herbal extracts in either OVX or ORX animals. Exercise combined with TLU improved resistance to fatigue in OVX animals, though A. turkestanica enhanced the grip strength in ORX mice. E. longifolia or TLU also reduced the ladder climbing time in ORX mice. Resistance exercise plus herbal extracts partly altered gastrocnemius fiber size frequencies in OVX or ORX mice. We provide novel data that tested ergogenic extracts, when combined with resistance exercise, improved early sarcopenia alterations in castrated male and female mice.     

Digitale Gesundheitsanwendungen (DiGA) in der ärztlichen und psychotherapeutischen Versorgung. Chancen und Herausforderungen aus Sicht der Leistungserbringer

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Versicherte haben seit 2019 einen gesetzlichen Anspruch auf Verordnung von digitalen Gesundheitsanwendungen (DiGA). Die...     

Human Diversity of Killer Cell Immunoglobulin-Like Receptors and Human Leukocyte Antigen Class I Alleles and Ebola Virus Disease Outcomes

We investigated the genetic profiles of killer cell immunoglobulin-like receptors (KIRs) in Ebola virus–infected patients. We studied the relationship between KIR–human leukocyte antigen (HLA) combinations and the clinical outcomes of patients with Ebola virus disease (EVD). We genotyped KIRs and HLA class I alleles using DNA from uninfected controls, EVD survivors, and persons who died of EVD. The activating 2DS4–003 and inhibitory 2DL5 genes were significantly more common among persons who died of EVD; 2DL2 was more common among survivors. We used logistic regression analysis and Bayesian modeling to identify 2DL2, 2DL5, 2DS4–003, HLA-B-Bw4-Thr, and HLA-B-Bw4-Ile as probably having a significant relationship with disease outcome. Our findings highlight the importance of innate immune response against Ebola virus and show the association between KIRs and the clinical outcome of EVD.     

ARCHITECT® urine-neutrophil gelatinase-associated lipocalin (u-NGAL) assay as new prognostic marker for clear cell Renal Cell Carcinoma (ccRCC) (preliminary results)

International Urology and Nephrology - Biomarkers for the diagnosis and monitoring treatment response of kidney cancer are urgently needed. Neutrophil gelatinase-associated lipocalin (NGAL) is a...     

Clinical features and outcome of maintenance hemodialysis patients with COVID-19 from a tertiary nephrology care center in Romania

Background There is limited information about the clinical characteristics, treatment and outcome of maintenance hemodialysis patients with COVID-19. Moreover, regional differences are also conceivable since the extend and severity of outbreaks varied among countries.Methods In this retrospective, observational, single-center study, we analyzed the clinical course and outcomes of 37 maintenance hemodialysis patients (median age 64 years, 51% men) hospitalized with COVID-19 from 24 March to 22 May 2020 as confirmed by real-time PCR.Results The most common symptoms at admission were fatigue (51%), fever (43%), dyspnea (38%) and cough (35%). There were 59% mild/moderate patients and 41% severe/critical patients. Patients in the severe/critical group had a significantly higher atherosclerotic burden since diabetic kidney disease and vascular nephropathies were the most common primary kidney diseases and eighty percent of them had coronary heart disease. Also, Charlson comorbidity score was higher in this group. At admission chest X-ray, 46% had ground-glass abnormalities. Overall, 60% patients received hydroxychloroquine, 22% lopinavir–ritonavir, 11% tocilizumab, 24% systemic glucocorticoids, and 54% received prophylactic anticoagulation. Seven (19%) patients died during hospitalization and 30 were discharged. The main causes of death were cardiovascular (5 patients) and respiratory distress syndrome (2 patients). In Cox regression analysis, lower oxygen saturation, anemia and hypoalbuminemia at admission were associated with increased mortality.Conclusions In conclusion, we observed a high mortality rate among maintenance hemodialysis patients hospitalized for COVID-19. Anemia, lower serum albumin and lower basal oxygen saturation at admission were factors associated with poor prognosis.     

Management of cervicofacial lymphatic malformations requires a multidisciplinary approach

Background/PurposeCervicofacial lymphatic malformations (CFLM) are rare, potentially life-threatening vascular anomalies, yet reports on multidisciplinary treatment strategies are lacking. We evaluated outcomes for CFLMs following sclerotherapy, surgical resection, and/or medical management.MethodsWe identified children with a CFLM at a vascular anomalies center from 2004 to 2019. Exclusion criteria: retro-orbital malformations, untreated malformations, patients without follow-up. Primary clinical outcome was contour improvement, with significance defined as LM volume reduction of > 50% by cross-sectional imaging.ResultsSixty-three children met inclusion criteria: 35 with macrocystic CFLMs, six with microcystic CFLMs, and 22 with mixed-type malformations. Mean post-intervention follow-up was 27.5 months. Fifty-eight patients underwent sclerotherapy (median: two treatments). Doxycycline and/or bleomycin were used in 95% of patients. After sclerotherapy, 97% of macrocystic CFLMs improved significantly compared to 82% of mixed and 67% of microcystic lesions. Sixteen children underwent surgical resection with 75% significantly improving; two additional patients were successfully treated with sclerotherapy after debulking surgery. Six children received sirolimus for microcystic disease, of which 33% significantly improved.ConclusionSclerotherapy is very effective for macrocystic components of CFLMs, albeit less so for microcystic disease. Microcystic CFLMs frequently require surgical resection. Sirolimus is a helpful therapeutic adjunct, particularly for microcystic lesions, but more study is needed.Level of EvidenceLevel II, prognosis study     

500 Consecutive Liver Transplants: The Outcomes of a New Transplantation Program in the Middle West of Brazil

IntroductionLiver transplantation is the standard treatment for end-stage liver disease. Brazil holds the third highest number of liver transplants performed per year, but center maldistribution results in high discrepancies in accessing this treatment. In 2012, an interstate partnership successfully implemented a new liver transplantation program in the middle west of Brazil. Here, we report the results of the first 500 liver transplants performed in this new program and discuss the impacts of a new transplant center in regional transplantation dynamics.MethodsWe reviewed data from the first 500 consecutive deceased donor liver transplants performed in the new program during an 8-year period. We analyzed data on patients’ clinical and demographic profiles, postoperative outcomes, and graft and recipient survival rates. Univariate survival analysis was conducted using log-rank tests to compare the groups.ResultsAlmost half (48%) of the procured organs and 40% of the recipients transplanted in our center were from outside our state. Recipient 30-day mortality was 9%. Overall recipient survival at 1 year and 5 years was 85% and 80%, respectively. Mortality was significantly associated with higher Model for End-Stage Liver Disease (P < .001) but not with the presence of hepatocellular carcinoma (P = .795).DiscussionThe new transplantation program treated patients from different regions of Brazil and became the reference center in liver transplantation for the middle west region. Despite the recent implementation, our outcomes are comparable to experienced centers around the world. This model can inspire the creation of new transplantation programs aiming to democratize access to liver transplantation nationwide.