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.     

Abuse of neuroleptic drug by psychiatric patients

Due to the depaminergic neurotrasmission in the mesocortical and mesolimbic reward systems, the neuroleptic drugs have been considered free from the risk of abuse or dependence because of their antidopaminergic properties. Here, two cases of neuroleptic abuse have been described and a possibility of reward circuits other than mesocortical and mesolimbic systems operational behind this phenomenon has been postulated. There is a need to clinically recognise the abuse potential of neuroleptic drugs.     

Diisocyanate asthma and gene-environment interactions with IL4RA, CD-14, and IL-13 genes.

BACKGROUND: Diisocyanate asthma (DA) affects 2% to 10% of exposed workers, yet the pathogenetic mechanisms underlying this disorder remain ill defined. OBJECTIVE: To determine if specific single nucleotide polymorphisms (SNPs) of interleukin 4 receptor alpha (IL4RA), IL-13, and CD14 promoter genes are associated with DA. METHODS: Sixty-two workers with DA confirmed by specific inhalation challenge (SIC) and 75 diisocyanate-exposed, SIC-negative workers were analyzed for SNPs associated with IL4RA, IL-13, and CD14 promoter genes. RESULTS: No associations were found with individual SNPs and DA. When stratified according to specific diisocyanate exposure, a significant association was found between IL4RA (I50V) II and DA among individuals exposed to hexamethylene diisocyanate (HDI) (odds ratio [OR], 3.29; 95% confidence interval [CI], 1.33-8.14; P = .01) only. Similarly, the IL4RA (I50V) II and IL-13 (R110Q) RR combination was significantly associated with DA in HDI-exposed workers (OR, 4.13; 95% CI, 1.35-12.68; P = .01), as was the IL4RA (I50V) II and CD14 (C159T) CT genotype combination (OR, 5.2; 95% CI, 1.82-14.88; P = .002) and the triple genotype combination IL4RA (I50V) II, IL-13 (R110Q) RR, and CD14 (C159T) CT (OR, 6.4; 95% CI, 1.57-26.12; P = .01). CONCLUSIONS: Gene-environmental interactions may contribute to the pathogenesis of DA, and gene-gene interactions may modulate this relationship.     

Fibrillary renal deposits and nephritis.

Fibrillary renal deposits and nephritis. The authors have studied 8 patients whose glomeruli contain abundant fibrils in their mesangial matrix and basement membranes. Although the location of these fibrils is very similar to that of amyloid, they are about twice the size of amyloid fibrils, averaging 20 nm in width, and fail to react as amyloid does with special stains. Immunofluorescence-microscopic studies are usually positive with antiserums to IgG, often IgM, and in some cases IgA, and also kappa and lambda light chains, C3, and C4. The fibrils are associated with diffuse mesangial widening and increased mesangial matrix strands. Although peripheral glomerular capillary walls appear to be spared initially, their eventual involvement leads to glomerular capillary collapse and glomerular obsolescence. Crescent formation occurred in 5 cases, focally in 3 and diffusely in 2. Tubular basement membrane involvement was seen in 1 case. These patients exhibit hematuria, and proteinuria, and often hypertension and renal insufficiency. Proteinuria was in the nephrotic range in 3 patients in whom involvement of glomerular capillary basement membranes was extensive. Unless electron microscopy is applied to renal biopsies, these cases may be considered to represent mesangiocapillary or rapidly progressive glomerulonephritis, or amyloidosis. The nature of these fibrils is as yet not determined. It is likely that they have been called "atypical amyloidosis" in the past.     

Insular carcinoma of thyroid--a case report

Insular carcinoma of thyroid (ICT) is a rare tumor, which accounts for 4-6% of thyroid malignancies. ICT arising from follicular cells of thyroid shows a characteristic insular growth pattern characterized by solid nests of tumor cells separated by vessels. A 52-year-old female presented with a huge swelling in midline of the neck with retrosternal extension. The patient was euthyroid. Near total thyroidectomy was done. Grossly, the tumour was involving both the lobes and isthmus of thyroid. Microscopic examination revealed features of insular carcinoma. On immunohistochemistry, tumour cells were positive for thyroglobulin and negative for calcitonin.     

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.     

Gelatinous transformation of bone marrow: a study of 43 cases

Gelatinous marrow transformation (GMT) is an uncommon and poorly recognized condition characterized by deposition of seromucinous gelatinous material in the bone marrow stroma. Forty-three cases of GMT were studied in a period of 4 years. There was male preponderance. Fourteen cases were in pediatric age group (less than 12 years). Majority of patients had a preceding history of anorexia, malnutrition and chronic debility. All the patients had anemia. Bone marrow biopsy revealed focal or diffuse GMT. Bone marrow aspirate showed metachromatic dense mucoid material with a few entrapped hematopoietic cells on Giemsa staining. The gelatinous material stained with alcian blue at pH 2.5.     

Case report: glomus tumor of the colon

Glomus tumors are tumors of pericytic origin and are usually found in the distal extremities. Glomus tumors have rarely been reported in viscera. The authors report a glomus tumor of the colon that caused rectal bleeding in a 40-yr-old man and was biopsied and excised endoscopically. The histology and immunohistochemical profile of the tumor are described and the literature on visceral glomus tumors is reviewed.     

Harnessing the potential of dystrophin‐related proteins for ameliorating Duchenne’s muscular dystrophy

Duchenne’s muscular dystrophy (DMD) is a fatal disease caused by mutations in the DMD gene that lead to quantitative and qualitative disturbances in dystrophin expression. Dystrophin is a member of the spectrin superfamily of proteins. Dystrophin itself is closely related to three proteins that constitute a family of dystrophin‐related proteins (DRPs): the chromosome 6‐encoded DRP or utrophin, the chromosome‐X encoded, DRP2 and the chromosome‐18 encoded, dystrobrevin. These proteins share sequence similarity and functional motifs with dystrophin. Current attempts at somatic gene therapy of DMD face numerous technical problems. An alternative strategy for DMD therapy, that circumvents many of these problems, has arisen from the demonstration that the DRP utrophin can functionally substitute for the missing dystrophin and its overexpression can rescue dystrophin‐deficient muscle. Currently, a promising avenue of research consists of identifying molecules that would increase the expression of utrophin and the delivery of these molecules to dystrophin‐deficient tissues as a means of DMD therapy. In this review, we will focus on DRPs from the perspective of strategies and issues related to upregulating utrophin expression for DMD therapy. Additionally, we will address the techniques used for anatomical, biochemical and physiological evaluation of the potential benefits of this and other forms of DMD therapy in dystrophin‐deficient animal models.