Toxic effects of interleukin-2-activated lymphocytes on vascular endothelial cells

IL-2-activated lymphocytes (LAK cells) show increased adherence to, and killing of, human vascular endothelial cells compared to resting lymphocytes. In the present work, we have found that supernatants from LAK cell cultures also are toxic to human umbilical vein endothelial cells (HUVEC) when tested for 48 h in a neutral red uptake assay. Recombinant TNF-alpha and IFN-gamma at high concentrations are also toxic under the same test conditions, and TNF-alpha was directly detected in LAK cell supernatants. An inconsistent inhibition of toxicity was found with anti-TNF-alpha whereas anti IFN-gamma antibodies had a partial inhibitory effect. The susceptibility of HUVEC to cellular killing by LAK cells could be up- and down-regulated with insulin-like growth factor I and IFN-gamma, respectively. It is concluded that damage to vascular endothelium during high dose IL-2 treatments may be partially related to an excessive production of lymphokines such as IFN-gamma and TNF-alpha. IFN-gamma may, in addition, be protective for HUVEC during cellular interactions with LAK cells.     

A human rights approach to low data reporting in clinical trials of psychiatric deep brain stimulation

The reporting of clinical trial data is necessary not only for doctors to determine treatment efficacy, but also to explore new questions without unnecessarily repeating trials, and to protect patients and the public from dangers when data are withheld. This issue is particularly salient in those trials involving invasive neurosurgical interventions, such as deep brain stimulation (DBS), for ‘treatment refractory’ psychiatric disorders. Using the federal database ClinicalTrials.gov, it was discovered that out of the completed or unknown‐status trials related to psychiatric DBS up to November 2018, only two had submitted results to ClinicalTrials.gov. These results suggest that, despite federal requirements to report clinical trial data, reporting on psychiatric DBS trials is problematically minimal. It is argued that a human rights approach to this problem establishes a legal and ethical foundation for the need to report clinical trial results in this area.     

Effect of experimentally-induced chronic hyperprolactinemia on insulin binding and antilipolytic response in adipocytes from male rats

Male Wistar rats with chronic hyperprolactinemia induced by grafting an anterior pituitary gland under the right kidney capsule were studied as experimental model. In these animals basal plasma glucose and insulin levels were unaltered. Epididymal adipocytes from hyperprolactinemic rats showed a significant increase in insulin binding at low unlabeled insulin concentrations. This increase in insulin binding can be principally attributed to an increase in the high affinity-low capacity binding sites, as demonstrated when Scatchard analysis was interpreted in terms of two types of insulin receptors. The dissociation constants (KD1 and KD2) were not different between the groups. The apparent insulin receptor affinity was also unchanged. Moreover, a decreased sensitivity to the antilipolytic effect of insulin was also obtained in adipocytes from hyperprolactinemic rats. These findings indicate that chronic hyperprolactinemia is able to increase high affinity insulin receptors in epididymal adipocytes, but tends to diminish the antilipolytic response, suggesting a lack of coupling between insulin binding and its biological activity in male adipose tissue. Several possible mechanisms involved in the process are suggested.     

The effect of Hordeum chilense and Triticum cytoplasms on anther culture response of tritordeum

With the aim of determining the effect of different cytoplasms on anther culture response, we analyzed anthers from different tritordeum lines with either Hordeum chilense, Triticum aestivum or T. turgidum cytoplasms for their response in vitro. The use of these tritordeum alloplasmic lines enabled cytoplasms belonging to two different genera to be compared for the first time. The results showed that the response from anthers of the tritordeum line containing T. turgidum cytoplasm was significantly lower than the response of the other two lines. This finding was encouraging from a practical point of view, since cytoplasms from both H. chilense and T. aestivum are preferred for the breeding of tritordeum.     

Cushing's syndrome due to bilateral adrenal macronodular hyperplasia with undetectable ACTH: cell culture of adenoma cells on extracellular matrix

A 59-year-old man developed Cushing's syndrome with massive bilateral adrenal macronodular hyperplasia. Plasma ACTH levels were undetectable both peripherally and in the inferior petrosal sinus. Computed tomography scans of his pituitary were normal. Hypercortisolism was not suppressed by high doses of dexamethasone. His adrenal cells were successfully isolated and grown on bovine corneal extracellular matrix. The cultured cells displayed strikingly rapid growth and hypersecretion of cortisol during incubation with control serum. Addition of the patient's serum to cultured fetal adrenal cells did not accelerate their growth. This was the first experience with our in vitro system in this rare clinical condition. The techniques described here may be used for future in vitro adrenal studies. These in vivo and in vitro data indicate that this patient's bilateral adrenal hyperfunction and growth were independent of ACTH.     

Antifungal γ-Pyrone and Isoprenylated Cyclohexanoids from the Fungus Beenakia informis

Chemical investigation of the extract of the macroscopic fungus Beenakia informis led to the isolation of a previously unreported γ-pyrone and two new isoprenylated cyclohexanoids, together with speciocin N. Their structures were elucidated spectroscopically and the absolute configuration was determined by comparison of the experimental vs. calculated ECD curves. Three of the compounds showed very good to moderate activity against phytopathogenic fungi.