Angiotensin-converting enzyme in sarcoid and chalazion granulomas of the conjunctiva

Angiotensin-converting enzyme (ACE) was studied immunohistochemically in conjunctival biopsies from 6 patients with systemic sarcoidosis, 4 patients with posterior non-sarcoid uveitis and in specimens from 4 patients with chalazion of the eyelid. Specimens with sarcoid granulomas showed intense ACE-positive immunoreactivity in epitheloid cells of the granuloma, whereas chalazion granulomas did not contain ACE-immunoreactivity. There was no difference in staining patterns between specimens without granulomas. Thus immunohistochemical staining for ACE may be of help in differentiating conjunctival granulomatous tissue of a chalazion from sarcoid granuloma.     

Renal allograft immunosuppression: II. A randomized trial of withdrawal of one drug in triple drug immunosuppression

Abstract. A prospective randomized study was conducted to evaluate the impact of four different conversion protocols on graft outcome in long-term follow-up. Between January 1986 and May 1987, 128 patients with first cadaveric kidney allografts were randomized at the time of transplantation to four treatment groups of 32 patients each, to be assigned 10 weeks post-transplantation. During the first 10 weeks, all patients received triple therapy with low-dose azathioprine (Aza), cyclosporin (CyA), and methylprednisolone (MP). After 10 weeks, one group continued with triple therapy (group A) while the three other groups received different combinations of two drugs, namely, Aza and CyA (group B), Aza and MP (group C), or CyA and MP (group D). Withdrawal of MP (group B) or especially of CyA (group C) was associated with 4/29 (14%) and 10/28 (36%) acute rejection episodes, respectively, for 60 days after conversion. All rejections were mild and reversible. There were no rejections after Aza withdrawal or in the group that continued on triple therapy during the corresponding time period. The most common reason for dropping out after withdrawal, for those patients who could not continue on the originally randomized medication, was azathioprine intolerance (n= 12). Five patients were switched back to triple therapy after CyA withdrawal due to rejection. Steroid intolerance was rare and CyA in low doses was very well tolerated. At 1 year there were no statistically significant differences in graft survival between groups A, B, C, and D-81 %, 88%, 88%, and 88%, respectively-or in patient survival-88%, 88%, 88%, and 97%, respectively. For those patients continuing with the originally randomized treatment protocol, there were no differences in patient or graft survival either, the means being 91% and 89%, respectively. The most common cause of death after withdrawal was cardiovascular in nature, and there were no more fatal infections under triple drug treatment than with double drug regimens. There were no statistically significant differences in mean serum creatinine values at 1 year. The median serum creatinine values for groups A, B, C, and D were 112, 132, 133, and 133 μmol/l, respectively. At 1 year the mean CyA dose in the groups that continued with CyA was 3. 5–4. 2 mg/kg per day and CyA concentrations were equal.     

Inhibition of phosphatidylinositol 3-kinase activity by association with 14-3-3 proteins in T cells.

Proteins of the 14-3-3 family can associate with, and/or modulate the activity of, several protooncogene and oncogene products and, thus, are implicated in regulation of signaling pathways. We report that 14-3-3 is associated with another important transducing enzyme, phosphatidylinositol 3-kinase (PI3-K). A recombinant 14-3-3 fusion protein bound several tyrosine-phosphorylated proteins from antigen receptor-stimulated T lymphocytes. PI3-K was identified by immunoblotting and enzymatic assays as one of the 14-3-3-binding proteins in resting or activated cells. Moreover, endogenous 14-3-3 and PI3-K were coimmunoprecipitated from intact T cells. Far-Western blots of gel-purified, immunoprecipitated PI3-K with a recombinant 14-3-3 fusion protein revealed direct binding of 14-3-3 to the catalytic subunit (p110) of PI3-K. Finally, anti-phosphotyrosine immunoprecipitates from activated, 14-3-3-overexpressing cells contained lower PI3-K enzymatic activity than similar immunoprecipitates from control cells. These findings suggest that association of 14-3-3 with PI3-K in hematopoietic (and possibly other) cells regulates the enzymatic activity of PI3-K during receptor-initiated signal transduction.     

A review of COVID-19 transmission dynamics and clinical outcomes on cruise ships worldwide,January to October 2020

BackgroundCruise ships provide an ideal setting for transmission of SARS-CoV-2, given the socially dense exposure environment.AimTo provide a comprehensive review of COVID-19 outbreaks on cruise ships.MethodsPubMed was searched for COVID-19 cases associated with cruise ships between January and October 2020. A list of cruise ships with COVID-19 was cross-referenced with the United States Centers for Disease Control and Prevention’s list of cruise ships associated with a COVID-19 case within 14 days of disembarkation. News articles were also searched for epidemiological information. Narratives of COVID-19 outbreaks on ships with over 100 cases are presented.ResultsSeventy-nine ships and 104 unique voyages were associated with COVID-19 cases before 1 October 2020. Nineteen ships had more than one voyage with a case of COVID-19. The median number of cases per ship was three (interquartile range (IQR): 1–17.8), with two notable outliers: the Diamond Princess and the Ruby Princess, which had 712 and 907 cases, respectively. The median attack rate for COVID-19 was 0.2% (IQR: 0.03–1.5), although this distribution was right-skewed with a mean attack rate of 3.7%; 25.9% (27/104) of voyages had at least one COVID-19-associated death. Outbreaks involving only crew occurred later than outbreaks involving guests and crew.ConclusionsIn the absence of mitigation measures, COVID-19 can spread easily on cruise ships in a susceptible population because of the confined space and high-density contact networks. This environment can create superspreader events and facilitate international spread.     

Jod als Heilmittel gegen kaltes Fieber

Ohne Zusammenfassung     

Expression of insulin-like growth factors IGF-I and IGF-II,and their receptors during the growth and megakaryocytic differentiation of K562 cells

Insulin-like growth factors (IGFs) I and II are critical regulators of cell proliferation and differentiation and most of the growth promoting properties of both ligands are mediated by IGF-I receptor (IGF-IR). In the present study we have investigated the role of IGFs in K562 cell line during normal growth and 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced megakaryocytic differentiation. Abundant expression of IGF-I, IGF-II and IGF-IR was demonstrated in resting cells and exogenous IGF-I and IGF-II increased 3H-thymidine incorporation in a dose dependent manner. In contrast, we found that basal growth of the cells was inhibited by using anti-IGF-IR mAb. Furthermore, also IGF-I and IGF-II induced DNA synthesis was significantly suppressed by anti-IGF-IR mAb. During megakaryocytic differentiation, expression of IGF-IR increased during first 12h, but after that the expression started to decrease together with IGF-I. Taken together, our data suggest that autocrine production of IGF-I and IGF-II may via IGF-IR play a significant role in the growth and megakaryocytic differentiation of K562 cells.