Syndecan-2 selectively regulates VEGF-induced vascular permeability.

Vascular endothelial growth factor (VEGF)- driven increase in vascular permeability is a key feature of many disease states associated with inflammation and ischemic injury, contributing significantly to morbidity and mortality in these settings. Despite its importance, no specific regulators that preferentially control VEGF-dependent increase in permeability versus its other biological activities, have been identified. Here we report that a proteoglycan Syndecan-2 (Sdc2) regulates the interaction between a transmembrane phosphatase DEP1 and VEGFR2 by controlling cell surface levels of DEP1. In the absence of Sdc2 or the presence of an antibody that blocks Sdc2-DEP1 interaction, increased plasma membrane DEP1 levels promote selective dephosphorylation of the VEGFR2 Y951 site that is involved in permeability control. Either an endothelial-specific Sdc2 deletion or a treatment with an anti-Sdc2 antibody result in a highly significant reduction in stroke size due to a decrease in intracerebral edema.

Influence of peanut matrix on stability of allergens in gastric-simulated digesta: 2S albumins are main contributors to the IgE reactivity of short digestion-resistant peptides.

BACKGROUND: Most food allergens sensitizing via the gastrointestinal tract are stable proteins that are resistant to pepsin digestion, in particular major peanut allergens, Ara h 2 and Ara h 6. Survival of their large fragments is essential for sensitizing capacity. However, the immunoreactive proteins/peptides to which the immune system of the gastrointestinal tract is exposed during digestion of peanut proteins are unknown. Particularly, the IgE reactivity of short digestion-resistant peptides (SDRPs; <10 kDa) released by gastric digestion under standardized and physiologically relevant in vitro conditions has not been investigated. OBJECTIVE: The aim of this study was to investigate and identify digestion products of major peanut allergens and in particular to examine IgE reactivity of SDRPs released by pepsin digestion of whole peanut grains. METHODS: Two-dimensional gel-based proteomics and shotgun peptidomics, immunoblotting with allergen-specific antibodies from peanut-sensitized patients, enzyme-linked immunosorbent inhibition assay and ImmunoCAP tests, including far ultraviolet-circular dichroism spectroscopy were used to identify and characterize peanut digesta. RESULTS: Ara h 2 and Ara h 6 remained mostly intact, and SDRPs from Ara h 2 were more potent in inhibiting IgE binding than Ara h 1 and Ara 3. Ara h 1 and Ara h 3 exhibited sequential digestion into a series of digestion-resistant peptides with preserved allergenic capacity. A high number of identified SDRPs from Ara h 1, Ara h 2 and Ara h 3 were part of short continuous epitope sequences and possessed substantial allergenic potential. CONCLUSION AND CLINICAL RELEVANCE: Peanut grain digestion by oral and gastric phase enzymes generates mixture of products, where the major peanut allergens remain intact and their digested peptides have preserved allergenic capacity highlighting their important roles in allergic reactions to peanut.

Peptidomics of an in vitro digested α-Gal carrying protein revealed IgE-reactive peptides.

The mammalian carbohydrate galactose-α1,3-galactose (α-Gal) causes a novel form of food allergy, red meat allergy, where patients experience severe allergic reactions several hours after red meat consumption. Here we explored gastric digestion of α-Gal glycoproteins using an in vitro model. Bovine thyroglobulin (BTG), a typical α-Gal carrying glycoprotein, was digested with pepsin. The resulting peptides were characterised by SDS PAGE, immunoblot and ImmunoCAP using sera from 20 red meat allergic patients. During pepsinolysis of BTG, a wide range of peptide bands was observed of which 14 to 17 kDa peptides remained stable throughout the gastric phase. The presence of the α-Gal epitope on the obtained peptides was demonstrated by an anti-α-Gal antibody and IgE from red meat allergic patients. The α-Gal digests were able to inhibit up to 86% of IgE reactivity to BTG. Importantly, basophil activation test demonstrated that the allergenic activity of BTG was retained after digestion in all four tested patients. Mass spectrometry-based peptidomics revealed that these peptides represent mostly internal and C-terminal parts of the protein, where the most potent IgE-binding α-Gal residues were identified at Asn1756, Asn1850 and Asn2231. Thus allergenic α-Gal epitopes are stable to pepsinolysis, reinforcing their role as clinically relevant food allergens.

Papillary Carcinoma in Mature Teratoma of Struma Ovarii.

A 62-year-old woman had the incidental finding of malignant struma ovarii following surgery for primary endometrial carcinoma. The patient had vaginal bleeding for one year. After gynecological examination, she was referred for fractional curettage which revealed endometrial cancer. The patient underwent total hysterectomy and bilateral adnexectomy. Histological findings of uterus confirm the presence of endometrial cancer. The left ovary showed the presence of mature teratoma with dominant thyroid tissue and focus of papillary carcinoma. Postoperatively she underwent radiation therapy and 3 months later total thyroidectomy. The stimulated thyroglobulin level was detectable. She was referred for radioiodine ablation with a dose of 3,7GBq 131-J. Post therapy scintigraphy shows pathological uptake of 131-J only in the neck. The patient continued treatment of endometrial cancer (external beam therapy). She is currently on suppressive hormone L-thyroxin therapy. Two months later hormonal status, thyroglobulin and antithyroglobulin antibodies showed optimal range.

Magnetic resonance imaging in diagnostic algorithm of solitary cold thyroid nodules.

PURPOSE: This study was performed to determine the role of magnetic resonance imaging (MRI) in a diagnostic algorithm for thyroid nodules. PATIENTS AND METHODS: Forty-four patients with solitary "cold" thyroid nodules were included in our study. MR images were analyzed visually. RESULTS: Benign nodules were shown as sharply marginated lesions classified by various signal intensity depending on nodule content. Thyroid carcinomas were shown as isointense or slightly hypointense lesions on T1-weighted images and hyperintense inhomogeneous lesions on T2-weighted images compared to normal thyroid tissue; following contrast, malignancies showed marked enhancement in most of the cases. CONCLUSION: In a thyroid diagnostic algorithm, conventional procedures such as ultrasound with fine needle aspiration and radionuclide scintigraphy should be performed first. In comparison with computed tomography (CT), MRI is superior because of better spatial resolution and the absence of ionizing radiation. MRI has its place in the staging of thyroid carcinoma and the preoperative assessment of the extent of malignant invasion of surrounding neck structures.

[Early diagnosis, therapy, follow-up and survival in patients with thyroid malignancies]. / Rana dijagnostika, terapija, pracenje i prezivljavanje bolesnika sa malignitetom stitaste zlezde.

UNLABELLED: The Aim of the paper was to give a review of an early diagnosis, therapy, follow-up and survival rate of patients with thyroid malignancy (TM). The paper presented the algorithm of early diagnosis: clinical, scintigraphic and ultrasonographic examination together with fine needle biopsy, cytologic analysis of the smear and biopsy ex tempore of the clear and suspected thyroid node to malignancy. Therapy of all TM forms was mainly surgical: postsurgical treatment was dependent on the type of malignancy: radioiodine 131-I, radiologic treatment, chemotherapy and radioimmunotherapy, (the latest one being in the phase of a clinical research). Follow-up was in accordance with the protocol and it was necessary because it contributes to the survival rate. In the presentation of survival rate for differentiated and medullar carcinomas we gave our results and literature data, while for the other malignancies only data from literature were presented. CONCLUSION: Only an early diagnosis of the nodular goiter together with an up-to-date treatment can cure TM patients in a high percentage and prevent development of a terminal stage of the disease which is extremely severe in all forms of this malignancy.

[131-I-lipiodol in therapy of liver carcinoma--methods and case report]. / 131-J-lipiodol u lecenju karcinoma jetre--metodologija i prikaz slucaja.

INTRODUCTION: Primary malignant liver tumors are successfully treated only by means of surgery, but no more than 10% of patients are candidates for surgical intervention. The rest receive only palliative treatment which is, as a rule, unsuccessful. 131I-Lipiodol therapy (commercial label LIPIOCISTM) applied to the hepatic artery through a catheter has been used since 1984, primarily for treatment of hepatocellular carcinoma (HCC). The aim of this paper is to review the methodology of 131J-Lipiodol treatment of primary liver carcinomas. This treatment was applied for the first time in Yugoslavia. CASE REPORT: A female patient, 46 years of age had an inoperable primary liver carcinoma. Since progression of the disease couldn't be controlled by chemotherapy, treatment with 131I-Lipiodol was indicated. After blocking the thyroid with Lugol, Sol. 2.22 GBq of 131I-Lipiodol was injected into hepatic artery via catheter, and the patient was isolated in a designated facility until discharged. Around 5 months later, second therapeutic dose of 1.11 GBq was administered. Early post-therapy complications were severe, but transient. After 131I-Lipiodol therapy, the tumor growth was stopped, but the patient's general condition slowly deteriorated. The patient died 7 months after receiving the first therapeutic dose. CONCLUSION: In the reported patient, 131I-Lipiodol therapy stopped the tumor growth within the liver and significantly prolonged survival compared to the expected, but no improvement in quality of life was achieved. This treatment methodology is very complex. Medical staff providing care for these patients is exposed to substantial irradiation.

[Use and efficacy of radioiodine therapy in the treatment of hyperthyroidism]. / Primena i efikasnost radiojodne terapije kao nacin lecenja hipertireoze.

Radioiodine (131J) therapy is a method of radical treatment for hyperthyroidism. In our study in the period 1971-1993, we administered radioiodine therapy in 163 patients with hyperthyroidism. We performed a long-term follow-up, from one month, to 21 years after the radioiodine therapy. The cured rate was 83.4%: euthyroid state was found in 43.6% of patients and hypothyroidism appeared in 39.9% of patients. After the radioiodine therapy hyperthyroidism was found in 16.6% of cases. Radioiodine therapy is very efficient, non-invasive, radical treatment of hyperthyroidism, not expensive and easy to administer. It has practically no immediate or long-term complications, except hypothyroidism.

Myocardial perfusion imaging using 99mTc-MIBI in patients with dilated cardiomyopathy--methodology and its clinical use.

The aim of the study was to demonstrate the methodology of investigation of myocardial perfusion and viability using 99mTc-MIBI in patients with dilated cardiomyopathy and to estimate its clinical use. Myocardial perfusion and viability were investigated by using the planar and SPECT scintigraphy and by estimating the wall motion of the myocardium. The foci of decreased myocardial viability were found in 7 patients. One patient had perfusion defect only at stress. Analyzing the patients data, by using the gated studies, we found various degrees of wall motion myocardial abnormalities.

[The role and value of perfusion parameters in clinical discrimination of "cold" thyroid nodes]. / Uloga i znacaj pokazatelja perfuzije u klinickoj diskriminaciji "hladnih" nodusa stitaste zlezde.

The aim of the study was to investigate if the perfusion parameters can be of value in differential diagnosis of "cold" thyroid nodes. This procedure was performed in 60 patients with "cold" unilateral nodes. The quantitative parameters of perfusion through the "cold" nodes were obtained by our own computer programme. The parameters of perfusion which gave the most impressive results are shown in this study. The ratio of perfusion between the node and healthy thyroid lobe was significantly higher in carcinomas (0.8) than in benign "cold" nodes: cysts (0.1), autommune thyroid diseases and benign solid goiters (0.4). The radioactivity increasing rate in node was significantly higher in carcinomas (2.7) than in benign nodes: Cysts (1.3), autoimmune thyroid diseases (1.5) and solid benign goiters (1.6). The ratio of radioactivity increasing rate between the node and healthy thyroid lobe was also significantly higher in carcinomas (0.9) than in other "cold" benign lesions (0.3).