Inactivation and Inhibition of Replication of the Enveloped Bacteriophage φ6 by Fatty Acids

The enveloped bacteriophage 6 has been shown to be an interesting model system for the study of chemical agents that might have specific antiviral effects against lipid-containing mammalian viruses. In this report, we describe two types of antiviral activity exhibited by several fatty acids against bacteriophage 6. Oleic acid (18:1) and palmitoleic acid (16:1) were potent inactivators of the virus. Treatment with either fatty acid at 50 μg/ml at 25 or 0°C for 30 min reduced the virus titer to about 0.1% of the initial titer. Oleic acid at a concentration as low as 3 μg/ml (~10⁻² mM) reduced the virus titer to <1% of the initial titer within 30 min. Ultracentrifugation analyses of ¹⁴C-amino acid- and ³²P-labeled virus treated with oleic acid indicated that the virion is largely disassembled by the treatment. Myristic acid (14:0) and palmitic acid (16:0) did not inactivate 6 at 50 μg/ml, but nevertheless did prevent 6 plaque production. Single-step virus growth experiments in which fatty acid was added at various times before or after infection indicated that it was an early stage of the 6 replication cycle that was inhibited by the presence of myristic acid and that the inhibition occurred only if the myristic acid concentration in the extracellular growth medium was 10 μg/ml. 6 could attach to its host cell in the presence of myristic acid at 50 μg/ml. We conclude that the fatty acids that prevent 6 replication probably do so by interfering with the entry of the viral genome into the host cell.     

Investigating the validity and usability of an interactive computer programme for assessing competence in telephone‐based mental health triage

Telephone‐based mental health triage services are frontline health‐care providers that operate 24/7 to facilitate access to psychiatric assessment and intervention for people requiring assistance with a mental health problem. The mental health triage clinical role is complex, and the populations triage serves are typically high risk; yet to date, no evidence‐based methods have been available to assess clinician competence to practice telephone‐based mental health triage. The present study reports the findings of a study that investigated the validity and usability of the Mental Health Triage Competency Assessment Tool, an evidence‐based, interactive computer programme designed to assist clinicians in developing and assessing competence to practice telephone‐based mental health triage.     

In vivo distribution of human adipose-derived mesenchymal stem cells in novel xenotransplantation models

The potential for human adipose-derived mesenchymal stem cells (AMSC) to traffic into various tissue compartments was examined using three murine xenotransplantation models: nonobese diabetic/severe combined immunodeficient (NOD/SCID), nude/NOD/SCID, and NOD/SCID/MPSVII mice. Enhanced green fluorescent protein was introduced into purified AMSC via retroviral vectors to assist in identification of cells after transplantation. Transduced cells were administered to sublethally irradiated immune-deficient mice through i.v., intraperitoneal, or subcutaneous injection. Up to 75 days after transplantation, tissues were harvested and DNA polymerase chain reaction (PCR) was performed for specific vector sequences as well as for human Alu repeat sequences. Duplex quantitative PCR using human beta-globin and murine rapsyn primers assessed the contribution of human cells to each tissue. The use of the novel NOD/SCID/MPSVII mouse as a recipient allowed rapid identification of human cells in the murine tissues, using an enzyme reaction that was independent of surface protein expression or transduction with an exogenous transgene. For up to 75 days after transplantation, donor-derived cells were observed in multiple tissues, consistently across the various administration routes and independent of transduction parameters. Tissue localization studies showed that the primary MSC did not proliferate extensively at the sites of lodgement. We conclude that human AMSC represent a population of stem cells with a ubiquitous pattern of tissue distribution after administration. AMSC are easily obtained and highly amenable to current transduction protocols for retroviral transduction, making them an excellent avenue for cell-based therapies that involve a wide range of end tissue targets.     

Posttransfusion graft-versus-host disease in Japanese newborns

BACKGROUND: Posttransfusion graft-versus-host disease (PT-GVHD) is underdiagnosed and underreported. Risk factors predisposing to PT-GVHD in newborn recipients, the clinical manifestations of the disease in newborns, and its mechanism are not well characterized. STUDY DESIGN and METHODS: A literature review identified 27 cases of PT-GVHD in newborns in Japan. Detailed information on volume of blood transfused, donor(s), and clinical course was analyzed. Infants with known immunodeficiency were excluded. RESULTS: Of 27 newborns, 20 were premature and 7 were full-term. Thirteen premature neonates were transfused frequently because of anemia; in 10 cases, exchange transfusion was performed. Fresh blood (相似文献   

Waning efficacy in a long-term AAV-mediated gene therapy study in the murine model of Krabbe disease

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Apical extracellular calcium/polyvalent cation-sensing receptor regulates vasopressin-elicited water permeability in rat kidney inner medullary collecting duct.

During antidiuresis, increases in vasopressin (AVP)-elicited osmotic water permeability in the terminal inner medullary collecting duct (tIMCD) raise luminal calcium concentrations to levels (> or = 5 mM) above those associated with the formation of calcium-containing precipitates in the urine. Calcium/polycation receptor proteins (CaRs) enable cells in the parathyroid gland and kidney thick ascending limb of Henle to sense and respond to alterations in serum calcium. We now report the presence of an apical CaR in rat kidney tIMCD that specifically reduces AVP-elicited osmotic water permeability when luminal calcium rises. Purified tIMCD apical membrane endosomes contain both the AVP-elicited water channel, aquaporin 2, and a CaR. In addition, aquaporin 2-containing endosomes also possess stimulatory (G(alpha q)/G(alpha 11) and inhibitory (G(alpha i1, 2, and 3)) GTP binding proteins reported previously to interact with CaRs as well as two specific isoforms (delta and zeta) of protein kinase C. Immunocytochemistry using anti-CaR antiserum reveals the presence of CaR protein in both rat and human collecting ducts. Together, these data provide support for a unique tIMCD apical membrane signaling mechanism linking calcium and water metabolism. Abnormalities in this mechanism could potentially play a role in the pathogenesis of renal stone formation.     

Concurrent community-acquired pneumonia with Legionella pneumophila and Streptococcus pneumoniae

Both Streptococcus pneumoniae and Legionella pneumophila are well defined causes of community-acquired pneumonia, and may be associated with substantial mortality. Optimal therapy consists of penicillin for the former organism and erythromycin for the latter. We have presented a case of pneumonia caused by simultaneous infection with both of these agents. Organisms were recovered either from blood or lung tissue. This case carries important implications for treatment of community-acquired pneumonia, and conceivably could explain some of the mortality that continues to be seen with pneumococcal pneumonia.     

Ileocolic anastomotic inflammation after resection for Crohn’s disease indicates disease recurrence: a histopathologic study

Abstract

Objectives: We performed a pathological pilot study to characterize the inflammation at the ileocolic anastomosis as Crohn’s disease or ischemia.

Methods and materials: Subjects were selected at random from a retrospective database of patients with Crohn’s disease and who had undergone an ileocolic resection with subsequent endoscopic assessment of the anastomosis and neo-terminal ileum. Pathology slides from the anastomotic mucosa, either from targeted biopsies or subsequent ileocolic resections, were re-assessed histologically for features of ischemia and of Crohn’s disease.

Results: Twenty-nine specimens from 8 patients were reviewed, including 12 ileocolic resection specimens and 17 sets of endoscopic biopsies. Twenty-seven of the 29 specimens, accounting for all of the patients, had evidence of CD-like features. In contrast, only 2 specimens, accounting for 2 of 8 patients, had histologic features of ischemia, and both specimens also had Crohn’s-like features.

Conclusion: To our knowledge this is the first study to specifically evaluate the pathology of ileocolic anastomoses in Crohn’s disease. It suggests that anastomotic inflammation is predominantly a manifestation of recurrent Crohn’s disease rather than of postoperative ischemia.