Transformed T lymphocytes infected by a novel isolate of human T cell leukemia virus type II

Human T cell leukemia virus type II (HTLV-II) has been isolated from a patient (Mo) with features of leukemic reticuloendotheliosis (LRE) and from a patient with acquired immunodeficiency syndrome (AIDS). We have obtained another isolate of HTLV-II from a patient (CM) with severe hemophilia A, pancytopenia, and a 14-year history of staphylococcal and candidal infections but no evidence of T cell leukemia/lymphoma, AIDS, or LRE. Fresh mononuclear cells and cultured lymphocytes from CM express retroviral antigens indistinguishable by molecular criteria from HTLV-IIMo. Leukocyte cultures from CM yield hyperdiploid (48,XY, +2, +19) continuous lymphoid lines; human fetal cord blood lymphocytes (CBL) are transformed by cocultivation with these CM cell cultures but retain normal cytogenetic constitution. Electron microscopic examination of the CM cultures and transformed CBL reveals budding of extracellular viral particles, intracellular tubuloreticular structures, and viral particles contained within intracellular vesicles. CM cell cultures and the transformed CBL do not require exogenous interleukin 2, have T cell cytochemical features and mature T helper phenotypes, and exhibit minimal T helper and profound T suppressor activity on pokeweed mitogen-stimulated differentiation of normal B cells. These characteristics, which are similar to those observed with the first HTLV-II isolate, may represent properties of all HTLV-II-infected T cells.     

Dose escalation and switching of biologics in ulcerative colitis: a systematic literature review in real-world evidence

Background: Biologics used to treat ulcerative colitis (UC) may lose their effect over time, requiring patients to undergo dose escalation or treatment switching, and systematic literature reviews of real-world evidence on these topics are lacking.

Aim: To summarize the occurrence and outcomes of dose escalation and treatment switching in UC patients in real-world evidence.

Methods: Studies were searched through MEDLINE, MEDLINE IN PROCESS, Embase and Cochrane (2006–2017) as well as proceedings from three major scientific meetings.

Results: In total, 41 studies were included in the review among which 35 covered dose escalation and 12 covered treatment switching of biologics. Tumor necrosis factor antagonist (anti-TNF) escalation for all patients included at induction ranged from 5% (6?months) to 50% (median 0.67?years) and 15.2% to 70.8% (8?weeks) for anti-TNF induction responders. Mean/median time to dose escalation on anti-TNF ranged from 1.84 to 11?months. The most common switching pattern, infliximab → adalimumab, occurred in 3.8% (median 5.6?years) to 25.5% (mean 3.3?years) of patients.

Conclusions: Dose escalation and treatment switching of biologics may be considered as indicators of suboptimal therapy suggesting a lack of long-term remission and response under current therapies.     

Why is 11beta-hydroxysteroid dehydrogenase type 1 facing the endoplasmic reticulum lumen? Physiological relevance of the membrane topology of 11beta-HSD1

11Beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) is essential for the local activation of glucocorticoid receptors (GR). Unlike unliganded cytoplasmic GR, 11beta-HSD1 is an endoplasmic reticulum (ER)-membrane protein with lumenal orientation. Cortisone might gain direct access to 11beta-HSD1 by free diffusion across membranes, indirectly via intracellular binding proteins or, alternatively, by insertion into membranes. Membranous cortisol, formed by 11beta-HSD1 at the ER-lumenal side, might then activate cytoplasmic GR or bind to ER-lumenal secretory proteins. Compartmentalization of 11beta-HSD1 is important for its regulation by hexose-6-phosphate dehydrogenase (H6PDH), which regenerates cofactor NADPH in the ER lumen and stimulates oxoreductase activity. ER-lumenal orientation of 11beta-HSD1 is also essential for the metabolism of the alternative substrate 7-ketocholesterol (7KC), a major cholesterol oxidation product found in atherosclerotic plaques and taken up from processed cholesterol-rich food. An 11beta-HSD1 mutant adopting cytoplasmic orientation efficiently catalyzed the oxoreduction of cortisone but not 7KC, indicating access to cortisone from both sides of the ER-membrane but to 7KC only from the lumenal side. These aspects may be relevant for understanding the physiological role of 11beta-HSD1 and for developing therapeutic interventions to control glucocorticoid reactivation.     

Inhibiting and disaggregating effect of gel-filtered Galega officinalis L. herbal extract on platelet aggregation

The in vitro inhibiting and disaggregating effect on platelet aggregation of a gel-fractionated herbal extract from Galega officinalis L. is examined. The obtained Sephadex G-25 filtered fraction was 35-36 times more active than the crude extract. The threshold concentration at which this fraction inhibits platelet aggregation (5-10% inhibition) by 50 microM adenosine 5'-diphosphate (ADP) is 4.5-5 microg per 1 ml platelet-rich plasma (PRP). At a concentration of 35 microg/ml PRP the fraction inhibits 50% of aggregation by ADP and at a concentration of 125 microg/ml PRP fully inhibits the aggregation of PRP by ADP. At a concentration of 40 microg/ml PRP the fraction inhibits initiation of platelet aggregation by 0.18 mg/ml collagen and at 50 microg/ml PRP inhibits the initiation of aggregation by 0.7 units/ml thrombin. The G-25 filtered fraction shows a strong disaggregating effect on aggregated PRP. At a concentration of 65-75 microg/ml PRP, the fraction is able to disaggregate the 50-53% of aggregated platelet-rich plasma by 50 microM ADP, and 25% of aggregated PRP by 0.18 mg/ml collagen.     

Computed tomography for cervical spine trauma. The impact of MDCT on fracture detection and dose deposition

A multidetector computed tomography (MDCT) was installed in our department. Referral rates, examination protocols and detection rates of abnormal findings in CT examinations for cervical spine trauma 6 months before and 6 months after MDCT installation were compared to look for changes in practice. Retrospective analysis of all CT cervical spine examinations in patients with multiple trauma over two contiguous 6-month periods: from July 2003 to December 2003 (helical CT) and from January 2004 to June 2004 (MDCT). Variables recorded were number of CT examinations performed, scan plane coverage and traumatic abnormalities detected. Phantom dosimetry measurements for cervical spine examination in both helical CT and MDCT were compared. One hundred and fifty four patients underwent cervical spine CT during these periods. Helical CT period: of 91 patients undergoing CT cervical spine examination for trauma, 65 (71%) were complete cervical examinations and 26 (29%) were level-specific examinations. Eight patients (9%) had cervical spine fracture, six of which were apparent on radiographs. Dose estimations for thyroid, lens and breast were 24.76, 1.86 and 0.21 mGy, respectively, for complete cervical spine examinations. MDCT period: of 63 patients who underwent CT cervical spine examination for trauma, 61 (97%) were complete examinations and 2 (3%) were level-specific examinations. Six patients (11%) had cervical spine fracture, three of which were apparent on radiographs. Dose estimations for thyroid, lens and breast were 75.8, 9.7 and 0.7 mGy, respectively, for complete cervical spine examinations, which were notably higher than those for helical CT. After installation of MDCT, clinical requests for complete examination of the cervical spine following trauma increased. This changing trend resulted in a significantly higher radiation dose to thyroid, lens and breast.     

Anti-aggregation activity of crude water extract of Galega officinalis L. fractionated on Sephadex G-25 and Sepharose 4B

The present study describes a method for preparation of biologically active fraction from crude water extract of Galega officinalis L. by gel filtration on Sephadex G-25 and Sepharose 4B. In an in vitro experiment (at a dose of 12.0 +/- 0.45 micrograms/ml) fractionated extracts inhibited adenosine diphosphate (ADF) induced platelet aggregation by 50%. Inhibitory effects on collagen (0.18 mg/ml) and thrombin (0.7 U/ml) induced platelet aggregation were observed at doses of 0.18 +/- 0.65 microgram/ml and 20 +/- 0.82 micrograms/ml, respectively. The optimum activity was observed at a temperature of 30-42 degrees C. It was found that the fraction contained 15.23% protein. As shown by amino acid analysis several amino acids (alanine, glycine, valine, lysine, asparagine, arginine and serine) accounted for 50% of its protein content. These amino acids formed tri- and tetrapeptides (RGD, RGDS, KRDS, RGDS), which inhibited platelet aggregation. The RGD and AGVD fibrinogen amino acid sequences responsible for the recognition and binding to the glycoprotein IIb/IIIa receptors consisted of the same amino acids.     

Ultrasound follow-up study of arthroscoped patients with gonitis.

The purpose of the present study was to evaluate by ultrasound methods and carry out a one-year follow-up study of synovial proliferation in the knee joint of patients with rheumatoid arthritis prior to and after arthroscopy and arthroscopic (AS) synovectomy. MATERIAL AND METHODS: 24 patients with a proven rheumatoid arthritis and affected knee joints were recruited for the study. Arthroscopic synovectomy of one of the affected joints was performed in all of them. The synovitis was evaluated clinically and ultrasonographically in 24 knee joints prior to the AS synovectomy and 7 days, and 3, 6 and 12 months after it. RESULTS: Either synovial thickening or villonodular proliferation in the knee joints were the findings in the examined patients using arthrosonography. All patient showed improvement of the disease activity index after the arthroscopic synovectomy and weakening of the baseline ultrasound evidence for synovial thickening and villonodular proliferation (p < 0.001). During the 12-month follow up study two patients were found at ultrasonography to have (without any clinical evidence for that) recurrence of the synovial thickening three months after arthroscopy. Ten patients had synovial thickening or villonodular proliferation recurrence during the 12 months of follow up with clinical evidence of gonitis; one case showed ultrasonographic evidence of hydrops. There was a complete consistency between the ultrasound and arthroscopic protocols with respect to the presence of synovial proliferation and intra-articular effusion. CONCLUSION: Arthosonography is an easy, safe, low-cost, non-invasive modality for diagnosis and follow-up of patients with rheumatoid arthritis prior to and after arthroscopic synovectomy and for assessment of the clinical prognosis in such patients.