Retinoic acid induces the differentiation of B cell hybridomas from patients with common variable immunodeficiency.

Human-human B cell hybridomas constructed from B lymphocytes of common variable immunodeficiency (CVI) patients and the nonsecreting cell line WIL2/729 HF consistently secrete low levels of Ig and appear to retain a defect characteristic of the CVI patient's B cells. We assessed the differentiative capacity of retinoic acid (RA) on these hybridomas, as well as on hybridomas constructed from normal B cells and from patients with selective IgA deficiency. RA at concentrations varying between 10(-5) and 10(-9) M augmented IgM secretion 4-20-fold from four of four CVI hybridomas tested, but did not affect Ig secretion from normal or IgA-deficiency hybridomas. In support of this elevated Ig secretion, RA enhanced the de novo synthesis of biosynthetically labeled light (kappa) and heavy (mu) Ig (up to 4- and 15-fold, respectively) in the CVI hybridoma line JK32.1. The increase in IgM synthesis/secretion could not be accounted for by RA-induced alteration in the cell cycle. In inducing this increase in IgM production, RA was found to affect two aspects of Ig gene expression: (a) the steady-state levels of heavy and light chain mRNAs were enhanced, and (b) the processing of mu heavy chain transcripts to the secreted mRNA form became favored over the membrane mRNA form. We also show that expression of Leu-17 (CD38), a surface marker that is re-expressed in the late pre-plasma stage of B cell development, was increased by RA from less than 20% to greater than 90% of the total cell population, with a concomitant 4-10-fold augmentation in the mean fluorescence intensity. Changes in both Leu-17 expression and de novo Ig synthesis were prominent by 24 h, but could be observed as early as 8 h after induction. Taken together, our study demonstrates that RA affects a marked alteration in the differentiated state of the CVI hybridoma clones. This finding suggests that retinoids can enhance the functional capabilities of B cells with defects in maturation and support further studies to evaluate their clinical potential in CVI

Hypoglossal schwannoma masquerading as a carotid body tumor.

Study Objective. To describe the clinical presentation, evaluation, and treatment of a hypoglossal schwannoma. Methods. We report an unusual case of a hypoglossal schwannoma presenting as a pulsatile level II neck mass at the bifurcation of the external and internal carotid arteries, mimicking a carotid body tumor. Radiologic findings are reviewed in detail. Results. A 59-year-old female presented to a tertiary care medical center with complaints of a pulsatile right-sided neck mass. An MRA of the neck was obtained demonstrating a 5 cm mass located at the carotid artery bifurcation and causing splaying of the internal and external carotids. Based on clinical presentation and imaging, a diagnosis of a carotid body tumor was conferred and the patient scheduled for excision. Intraoperatively, the mass was noted to arise from the hypoglossal nerve, remaining independent of the carotid artery. On histopathologic analysis, the mass was determined to be consistent with hypoglossal schwannoma. Conclusion. Though rare, the hypoglossal schwannoma should remain a consideration in the evaluation of a parapharyngeal space mass. As this report demonstrates, the clinical and radiologic presentation of a hypoglossal schwannoma may closely mimic that of the more common carotid body tumor

The Reliability of an Isokinetic Dynamometer and Force Gauge in Measuring Core Strength

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Hypoglossal Schwannoma Masquerading as a Carotid Body Tumor

Study Objective. To describe the clinical presentation, evaluation, and treatment of a hypoglossal schwannoma. Methods. We report an unusual case of a hypoglossal schwannoma presenting as a pulsatile level II neck mass at the bifurcation of the external and internal carotid arteries, mimicking a carotid body tumor. Radiologic findings are reviewed in detail. Results. A 59-year-old female presented to a tertiary care medical center with complaints of a pulsatile right-sided neck mass. An MRA of the neck was obtained demonstrating a 5 cm mass located at the carotid artery bifurcation and causing splaying of the internal and external carotids. Based on clinical presentation and imaging, a diagnosis of a carotid body tumor was conferred and the patient scheduled for excision. Intraoperatively, the mass was noted to arise from the hypoglossal nerve, remaining independent of the carotid artery. On histopathologic analysis, the mass was determined to be consistent with hypoglossal schwannoma. Conclusion. Though rare, the hypoglossal schwannoma should remain a consideration in the evaluation of a parapharyngeal space mass. As this report demonstrates, the clinical and radiologic presentation of a hypoglossal schwannoma may closely mimic that of the more common carotid body tumor

Carcinogenic Effects in a Phenylketonuria Mouse Model

Phenylketonuria (PKU) is a metabolic disorder caused by impaired phenylalanine hydroxylase (PAH). This condition results in hyperphenylalaninemia and elevated levels of abnormal phenylalanine metabolites, among which is phenylacetic acid/phenylacetate (PA). In recent years, PA and its analogs were found to have anticancer activity against a variety of malignancies suggesting the possibility that PKU may offer protection against cancer through chronically elevated levels of PA. We tested this hypothesis in a genetic mouse model of PKU (PAHenu2) which has a biochemical profile that closely resembles that of human PKU. Plasma levels of phenylalanine in homozygous (HMZ) PAHenu2 mice were >12-fold those of heterozygous (HTZ) littermates while tyrosine levels were reduced. Phenylketones, including PA, were also markedly elevated to the range seen in the human disease. Mice were subjected to 7,12 dimethylbenz[a]anthracene (DMBA) carcinogenesis, a model which is sensitive to the anticancer effects of the PA derivative 4-chlorophenylacetate (4-CPA). Tumor induction by DMBA was not significantly different between the HTZ and HMZ mice, either in total tumor development or in the type of cancers that arose. HMZ mice were then treated with 4-CPA as positive controls for the anticancer effects of PA and to evaluate its possible effects on phenylalanine metabolism in PKU mice. 4-CPA had no effect on the plasma concentrations of phenylalanine, phenylketones, or tyrosine. Surprisingly, the HMZ mice treated with 4-CPA developed an unexplained neuromuscular syndrome which precluded its use in these animals as an anticancer agent. Together, these studies support the use of PAHenu2 mice as a model for studying human PKU. Chronically elevated levels of PA in the PAHenu2 mice were not protective against cancer

Kožna dekontaminacija živčanoga bojnog otrova sarina s apsorpcijskim pripravkom u uvjetima in vivo

Our Institute’s nuclear, biological, and chemical defense research team continuously investigates and develops preparations for skin decontamination against nerve agents. In this in vivo study, we evaluated skin decontamination efficacy against sarin by a synthetic preparation called Mineral Cationic Carrier (MCC®) with known ion exchange, absorption efficacy and bioactive potential. Mice were treated with increasing doses of sarin applied on their skin, and MCC® was administered immediately after contamination. The results showed that decontamination with MCC® could achieve therapeutic efficacy corresponding to 3 x LD50 of percutaneous sarin and call for further research.Istraživački tim NBKO (nuklearno-biološko-kemijske obrane) radi na pronalasku i razvoju pripravka za dekontaminaciju kože od živčanih bojnih otrova. Cilj ovog istraživanja bio je ispitati dekontaminacijska svojstva (adsorpcijska i/ili kemisorpcijska) pripravka MCC® rabeći živčani bojni otrov sarin kao kožni kontaminant u uvjetima in vivo. MCC® je sintetski pripravak koji je biokemijski aktivan i ima ionskoizmjenjivačka i adsorpcijska svojstva. Istraživanje u uvjetima in vivo napravljeno je na miševima aplikacijom rastućih doza sarina na kožu životinje. Pripravak MCC® uporabljen je kao kožni dekontaminant neposredno nakon kožne kontaminacije sarinom. Istraživanja su pokazala da pripravak MCC® posjeduje adsorpcijska svojstva, ujedno važna za dekontaminaciju živčanih bojnih otrova. Eksperimenti u uvjetima in vivo na miševima (NOD-soj) pokazali su da se dekontaminacijom pripravkom MCC® može postići terapijski učinak od 3 LD50 (perkutano, sarin)