T-cell phenotypic and functional changes associated with social subordination and gene polymorphisms in the serotonin reuptake transporter in female rhesus monkeys

Increased vulnerability to psychosocial stressors likely predisposes individuals to decreased immune function and inability to control pathogens. While many factors influence the susceptibility to psychosocial stress, genetic polymorphisms may modify individual reactivity to environmental stressors. The present study evaluated how immune function was altered by the interaction of in polymorphisms in the gene that encodes the serotonin reuptake transporter (5HTT) and the psychosocial stress imposed by social subordination in adult female rhesus monkeys. Subjects were dominant and subordinate females that carried both alleles of the long promoter variant (l/l) of the 5HTT gene, and dominant and subordinate that had at least one allele for the short promoter length variant (l/s or s/s, s-variant). Plasma cortisol was higher in subordinate females in response to a social separation paradigm, confirming their increased reactivity to psychosocial stressors. Subordinate females exhibited increased T-cell activation and proliferation regardless of genotype. Despite these higher levels of T-cell proliferation and activation, subordinate females showed significantly lower frequency of T-cells. This latter finding may be due to an increased susceptibility to cell death, as indicated by higher levels of annexin-V+ CD4+ and CD8+ T-cells in s-variant subordinate compared to dominant females. These findings indicate that subordinate rhesus monkeys with the s-variant 5HTT genotype exhibit decreased T-cell numbers perhaps compromising their ability to mount an immune response to pathogens. These data underscore the importance for considering gene polymorphisms that influence emotional reactivity to better understand susceptibility to disease.     

Glioblastoma with adipocyte-like tumor cell differentiation--histological and molecular features of a rare differentiation pattern

We report on three adult patients with primary glioblastomas showing prominent adipocytic (lipomatous) differentiation, hence referred to as "glioblastomas with adipocyte-like tumor cell differentiation." Histologically, the tumors demonstrated typical features of glioblastoma but additionally contained areas consisting of glial fibrillary acidic protein (GFAP)-positive astrocytic tumor cells resembling adipocytes, that is, containing large intracellular lipid vacuoles. Comparative genomic hybridization (CGH) and focused molecular genetic analyses demonstrated gains of chromosomes 7, losses of chromosomes 9 and 10, as well as homozygous deletion of p14^ARF in one of the tumors. The second tumor showed gains of chromosomes 3, 4, 8q and 12 as well as losses of chromosomes 10, 13, 15q, 19 and 22. In addition, this tumor carried homozygous deletions of CDKN2A and p14^ARF as well as point mutations in the TP53 and PTEN genes. The third tumor also had a mutation in the PTEN gene. None of the tumors demonstrated EGFR , CDK4 or MDM2 amplification. Taken together, our results define a rare glioblastoma differentiation pattern and indicate that glioblastomas with adipocyte-like tumor cell differentiation share common molecular genetic features with other primary glioblastomas.     

Preimplantation genetic diagnosis for mitochondrial DNA disorders: ethical guidance for clinical practice

Although morally acceptable in theory, preimplantation genetic diagnosis (PGD) for mitochondrial DNA (mtDNA) disorders raises several ethical questions in clinical practice. This paper discusses the major conditions for good clinical practice. Our starting point is that PGD for mtDNA mutations should as far as possible be embedded in a scientific research protocol. For every clinical application of PGD for mtDNA disorders, it is not only important to avoid a ‘high risk of serious harm'' to the future child, but also to consider to what extent it would be possible, desirable and proportional to try to reduce the health risks and minimize harm. The first issue we discuss is oocyte sampling, which may point out whether PGD is feasible for a specific couple. The second issue is whether one blastomere represents the genetic composition of the embryo as a whole – and how this could (or should) be investigated. The third issue regards the cutoff points below which embryos are considered to be eligible for transfer. We scrutinize how to determine these cutoff points and how to use these cutoff points in clinical practice – for example, when parents ask to take more or less risks. The fourth issue regards the number of cycles that can (or should) justifiably be carried out to find the best possible embryo. Fifth, we discuss whether follow-up studies should be conducted, particularly the genetic testing of children born after IVF/PGD. Finally, we offer the main information that is required to obtain a truly informed consent.     

Extra-adrenal Composite Paraganglioma with Ganglioneuroma Component Presenting as a Pancreatic Mass

Paragangliomas may have composite forms in which they combine features of a typical paraganglioma with those of a neural component consisting of either neuroblastoma, ganglioneuroblastoma, or ganglioneuroma. These variants are rare and generally located in the adrenal. Herein, we describe a retroperitoneal, extra-adrenal composite paraganglioma–ganglioneuroma of a 57-year-old woman. Radiological evaluation revealed a nodular mass with apparent pancreatic location, with findings suggestive of an endocrine tumor, yielding the diagnosis of a pancreatic endocrine tumor. At histology the neoplasm, strictly adhering to the external surface of the pancreatic gland but well demarcated, displayed a main central region with typical paraganglioma features and cells arranged in cords and in a nesting “zellballen” pattern, positive for neuroendocrine markers, and a distinct peripheral area consisting of dense bundles of wavy spindled Schwann cells, with scattered ganglionic cells.     

Hepatitis B and liver transplantation: 2008 update

The ultimate goal of treatment is suppression of viral replication to undetectable HBV-DNA levels prior to and after liver transplantation (LT) to prevent infection of the newly transplanted liver. Most published data are available from therapy with lamivudine (LAM) in pre- and post-transplant HBV patients. Add-on therapy with adefovir dipivoxil (ADV) in pre-transplant LAM-resistant patients has been shown to represent an effective antiviral strategy leading to hepatic recompensation in many cases and, eventually, removal from the waiting list. Newer nucleos(t)ide analogues such as entecavir, tenofovir and telbivudine have shown lower resistance rates than LAM and more antiviral potency in studies in the non-transplant setting. Combined hepatitis B immune globulin (HBIG) and nucleos(t)ide analogue therapy have been widely adopted as the most effective treatment strategy against recurrent HBV disease after LT. Many programs have evaluated lower doses or a shorter duration of HBIG and intramuscular versus intravenous routes of administration. Active immunisation using recombinant HBV vaccines, including the S, pre-S1 and pre-S2 regions, and those with immunostimulatory adjuvants, seem to be more immunogenic than the currently available vaccines and have been used in studies to replace HBIG. Furthermore, it has been shown that immune memory against HBV can be adoptively transferred from organ donors to transplant recipients. Nucleos(t)ide analogue combination therapies might provide an alternative to the current treatment paradigm with costly HBIG; however, experience with this new treatment regimen is very limited and controlled clinical studies are urgently warranted to investigate its safety and efficacy and to determine which nucleos(t)ide analogue combinations will be the most promising in the long term after LT.     

Improvement of the live vaccine strain Salmonella enterica serovar Typhi Ty21a for antigen delivery via the hemolysin secretion system of Escherichia coli

The attenuated Salmonella enterica serovar Typhi strain Ty21a (Ty21a) is the only attenuated live oral vaccine against typhoid fever. Ty21a is also an attractive carrier for the delivery of heterologous antigens. We have used Ty21a for antigen delivery via the hemolysin (HlyA) secretion system of Escherichia coli, the prototype of the type I secretion system (T1SS). In this study, we identified by genetic complementation that the specific mutation of rpoS correlated with the hemolysin production of strain Ty21a. We furthermore showed that complementation with a plasmid encoding rfaH, which is described to be a downstream target of rpoS, led to increased expression and secretion of hemolysin. Finally, we demonstrated a significant enhancement of antibody responses against the heterologous HlyA antigen of Ty21a after immunization of mice with rfaH complemented S. typhi strain secreting HlyA compared with the same strain without rfaH plasmid.     

Physical characteristics of the back are not predictive of low back pain in healthy workers: A prospective study

Background  

In the working population, back disorders are an important reason for sick leave and permanent work inability. In the context of fitting the job to the worker, one of the primary tasks of the occupational health physician is to evaluate the balance between work-related and individual variables. Since this evaluation of work capacity often consists of a physical examination of the back, the objective of this study was to investigate whether a physical examination of the low back, which is routinely performed in occupational medicine, predicts the development of low back pain (LBP).     

False aneurysm of the interosseous artery and anterior interosseous syndrome - an unusual complication of penetrating injury of the forearm: a case report

Background  

Palsies involving the anterior interosseous nerve (AIN) comprise less than 1% of all upper extremity nerve palsies.     

Study of the microcirculation in hDAF transgenic rat livers xenoperfused with human blood

Abstract: Background: The microcirculation was assessed in the livers of human decay accelerating factors (hDAF) and wild‐type transgenic rats by fluorescent intravital microscopy, histology and histomorphology to determine the benefits of hDAF expression for the microcirculation of a rat liver xenograft perfused with human blood. Methods: Male hDAF transgenic rats (group A; n = 20) and wild‐type Sprague–Dawley rats (group B; n = 20) were xenoperfused with human blood, while other male wild‐type Sprague–Dawley rats (group C; n = 10) were perfused with allogeneic blood. Following plasma and leukocyte staining with fluorescein sodium, and platelet staining with rhodamine, the right lobe of the liver was assessed by intravital microscopy, counting the numbers of perfused sinusoids and leukocytes adhering to the endothelium per mm², and calculating the acinar perfusion index (Pi). The liver underwent histological assessment at the end of each experiment. Mean ± SEM values were calculated and the Mann–Whitney U‐test was used for statistical analysis. Results: The number of perfused sinusoids was higher in the group of hDAF rat livers (group A) and controls (group C) than in the group of non‐transgenic rat livers perfused with human blood (group B) (P < 0.05), although only group C still had a significantly more perfused sinusoids than the other groups after 90 min of perfusion (P < 0.05). The acinar perfusion index was higher in groups A and C than in group B (P < 0.05); here again, only group C still had a significantly higher Pi than group B after 90 min of perfusion (P < 0.05). There was a massive accumulation of leukocytes that peaked after 5 min and persisted throughout the perfusion in all three groups. Histology showed portal and subendothelial hepatic vein hemorrhage, necrosis and inflammatory reaction, which were particularly evident in group B. Conclusion: In our study, rat livers transgenic for hDAF were better protected against early tissue damage by perfusion with human blood, but this did not result in a longer xenograft survival.