Alterations in free radical scavenger system profile of type I diabetic rat brain

The activities of the enzymes related to glutathione synthesis, degradation, and functions as well as reactive oxygen scavenging enzymes were analyzed in different brain regions, such as cerebral hemisphere, cerebellum, brainstem, thalamus, and hypothalamus after 1 and 3 mo of streptozotocin-induced diabetes in rats. Parallel studies were also made in age-matched control rats and insulin-treated diabetic rats. The content of glutathione (GSH) and its synthesizing enzyme γ-glutamylcystein synthetase and also superoxide dismutase (SOD) and catalase activities (reactive oxygen scavenging enzymes) were significantly decreased from almost all the brain regions studied. However, glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), γ-glutamyl transpeptidase (γ-GTP), and glutamine synthetase (GS) activities were increased in the diabetic rat brain. Insulin treatment to the diabetic rats resulted in partial to full recovery in these enzymes activities. The present results emphasize the potentially serious alterations of brain free radical scavenger system in uncontrolled Type I diabetes.     

Beta-2-glycoprotein specificity of human anti-phospholipid antibody resides on the light chain: a novel mechanism for acquisition of cross-reactivity by an autoantibody

We have recently shown that the anti-cardiolipin activity of human anti-phospholipid antibody UK4 (lambda) resides on its heavy chain. We now show that UK4 possesses strong reactivity to the plasma-protein beta2-Glycoprotein I (beta2-GPI) also. Utilizing chain shuffling experiments involving an unrelated anti-p185 antibody 4D5 (kappa) with no reactivity to beta2-GPI, we now demonstrate that both the constructs possessing the auto-antibody-derived light chain exhibited significant binding to beta2-GPI. However, the construct possessing UK4 heavy chain in association with 4D5 light chain, exhibited no anti-beta2-GPI activity. Furthermore, there was a low increase (approximately 10%) in the binding of UK4 to cardiolipin in the presence of beta2-GPI. The results demonstrate that anti-beta2-GPI activity resides on UK4 light chain and, importantly, this activity could be transferred to a novel antibody construct via the light chain alone. Computer-generated models of the three-dimensional structures of UK4 and its hybrids, suggest predominant interaction of UK4 light chain with domain IV of beta2-GPI. Molecular docking experiments highlight a number of potential sites on beta2-GPI for interaction of UK4 and indicate as to how beta2-GPI recognition may occur primarily via the autoantibody light chain. The study provides first demonstration of the occurrence of anti-phospholipid and anti-beta2-GPI activities separately on heavy and light chains of an autoantibody. The possible mechanisms that such antibodies may employ to recognise their antigens, are discussed.     

Xanthomatous Hypophysitis: A Novel Entity of Obscure Etiology

We report a case of xanthomatous hypophysitis, a recently described entity of obscure etiology affecting the pituitary gland, in a 43-yr-old women. Histologically it is characterized by infiltration of the anterior pituitary by foamy histiocytes which are strongly immunoreactive for CD68 (histiocytic marker) and are immunonegative for S100 and CD1a. Electron microscopy revealed histiocytes with abundant cytoplasmic lipid droplets and membrane bound vacuoles. Fragments of intact anterior pituitary with preserved vascular and reticulin networks are seen. Xanthomatous hypophysitis resembles neoplasm on clinical and radiologic grounds.     

Role of lateral neck dissection in cancers of the larynx and hypopharynx with No neck

Radical neck dissection is a standard procedure carried out for the teatment of palpable nodes in the neck but if carried out electively in cases where there are no palpable nodes in the neck it is considered to be an overtreatment with its associated morbity. Lateral neck dissection was carried out on twenty patients who had T31 T4 lesion of the larynx and hypophar-vnx with NO neck. The dissection entails removal of Level II. III and IV nodes. Occult metastasis 80% and 85% respectively. The mean follow up was 13 monts. It appears from our study that elective lateral neck dissection is a promising and safe procedure and may be useful as an important prognostic tool in sampling the lymph nodes and predicting recurrences in the neck.     

The Effect of Conformation on Membrane Permeability of an Acyloxyalkoxy-linked Cyclic Prodrug of a Model Hexapeptide

Purpose. To determine the different conformations of the acyloxyalkoxy-linked cyclic prodrug 1 of the model hexapeptide 2 in solution and to investigate the relationship between these solution conformations and the cellular permeability characteristics of this prodrug. Methods. Two-dimensional Homonuclear Hartmann-Hahn spectroscopy, Rotating-Frame Overhouser effect spectroscopy, circular dichroism and molecular dynamics simulations were used to find the solution conformers of cyclic prodrug 1. Results. Our spectroscopic findings suggest that cyclic prodrug 1 exhibits a major and a minor conformer in solution. The major conformer appears to have a well-defined secondary structure, which involves a -turn and 4 1 intramolecular hydrogen bond, creating a compact structure with a reduced average hydrodynamic radius compared to the model hexapeptide 2. Conclusions. The increased ability of cyclic prodrug 1 to permeate membranes compared to the model hexapeptide 2 could be due to reduction in the average hydrodynamic radius of the molecule facilitating paracellular flux and/or the reduction in the hydrogen bonding potential facilitating transcellular flux.     

Cystosarcoma phyllodes: Our institutional experience

Twenty‐six patients of Cystosarcoma phyllodes, treated between July 1994 and July 2001, were analysed retrospectively. Median age at presentation was 38 years (range 13?61 years). Mean size of the lesion was 6 cm. There were 77% left‐sided lesions and 23% right‐sided lesions. Histologically, 58% lesions were benign, 11% borderline and 31% malignant lesions. All patients underwent definitive surgical procedure in the form of wide local excision or mastectomy. Four patients received postoperative radiotherapy. Median follow‐up period was 35 months. Six patients showed recurrence, and four of these were malignant. Median disease‐free survival period was 34 months.