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.     

Synthesis and Antitumour Activity of New Derivatives of Flavone-8-acetic Acid (FAA). Part 1: 6-Methyl Derivatives

A range of 17 derivatives of flavone-8-acetic acid (FAA) with a 6-methyl substituent have been prepared and their anti-tumour activity evaluated in vitro against a panel of human and murine tumour cell lines and in vivo against MAC 15A. While many of the compounds show activity comparable to FAA in vitro, this essentially disappears in vivo, possibly due to degradation before the compounds can reach the tumour site.     

TNFα Inhibits Schwann Cell Proliferation, Connexin46 Expression, and Gap Junctional Communication

Schwann cell responses to nerve injury are stimulated, in part, by inflammatory cytokines. This study compares changes in the phenotype of cultured Schwann cells after exposure to the cytokine tumor necrosis factor (TNF)-α or the mitogen neu differentiation factor (NDF)-β. TNFα inhibited proliferation in a dose-dependent manner without altering Schwann cell survival. TNFα also reduced both gap junctional conductance and Lucifer yellow dye coupling between Schwann cells. Moreover, both P₀and glial fibrillary acidic protein (GFAP) immunoreactivity were reduced. By contrast, NDFβ initially had little effect on cell division although it reduced junctional coupling within 8 h. However, by 48 h, NDFβ stimulated proliferation with a concomitant increase in coupling. Dividing Schwann cells (BrdU⁺) were preferentially dye coupled compared to nondividing cells, indicating an association between proliferation and coupling. Moreover, cultured Schwann cells expressed connexin46 mRNA and protein, and changes in the levels of the protein correlated with the degree of proliferation and coupling. The data thus provide evidence for cytokine-induced modulation of Schwann cell antigenic phenotype, proliferation, and gap junction properties. These observations suggest that enhanced gap junctional communication among Schwann cells after nerve injury could help to coordinate cellular responses to the injury, and that TNFα may be a signal which terminates proliferation as well as junctional communication.     

Multiplex PCR assay for rapid identification of oculopathogenic adenoviruses by amplification of the fiber and hexon genes

Eye infections caused by adenovirus (Ad) often result in nosocomial infections and community epidemics with significant rates of morbidity. No antiviral agent effective against Ad is yet available for clinical use. Therefore, early diagnosis is still the mainstay for patient management and the prevention of epidemics. A multiplex PCR assay based on amplification of a combination of the fiber and hexon genes which can identify the six important oculopathogenic serotypes of Ads (Ad serotype 3[Ad3], Ad4, Ad7, Ad8, Ad19, and Ad37) in a single-tube amplification reaction was developed. Ad serotypes could be distinguished by the different amplicon sizes. The assay correctly identified prototype strains as well as isolates in clinical specimens. In comparison with a previously described PCR-restriction fragment polymorphism method, our assay gave unequivocal results for clinical specimens. Our multiplex PCR has the potential to serve as a rapid and cost-effective tool for the typing of important ocular Ads.     

Megakaryocytes in pleural and peritoneal fluids: prevalence, significance, morphology, and cytohistological correlation.

Over a period of 22 years, 4844 pleural and peritoneal fluids from 3279 patients were examined cytologically. Megakaryocytes were found in the fluids from five patients. The clinical diagnoses in the five patients were agnogenic myeloid metaplasia, chronic myeloid leukaemia, and lymphocytic lymphoma. All of these patients had persistent serous effusions. Megakaryocytes in serous fluids occurred in three forms: (1) a large type with abundant cytoplasm and multilobed nuclei, (2) a smaller type with a high nucleocytoplasmic ratio and unlobed nuclei, and (3) anucleate cytoplasmic masses. Foci of agnogenic myeloid metaplasia found on the serous surfaces at necropsy of two patients contained megakaryocytes similar to those in the corresponding effusions. The clinical course of our patients confirmed that the presence of megakaryocytes in serous fluids signifies an advanced haematopoietic malignancy.     

Heart-focused anxiety,illness beliefs,and behavioral impairment: Comparing healthy heart-anxious patients with cardiac and surgical inpatients

Psychological features and complaints of persons presenting to medical settings with heart-focused anxiety and noncardiac chest pain are poorly understood. Comparing 20 healthy heart-anxious patients to cardiac and surgical inpatients and nonpatient controls, we found that healthy heart-anxious patients (a) were as afraid of chest pain and heart palpitations as inpatients with heart disease, (b) were as incapacitated by symptoms and using medical services as much as both inpatient groups; and (c) reported higher levels of cardiac disease conviction, heart awareness, and behaviors designed to protect their heart than surgical patients and nonpatients. Compared to all other groups, healthy heart-anxious patients reported more panic and other anxiety disorders, hypochondriacal beliefs, physical symptoms, obsessive-compulsive concerns, and negative affect. Following a hyperventilation test, heart-anxious patients also indicated more distressing symptoms and thoughts, and felt less safe and in control than surgical patients and nonpatients. Results support efforts for a timely recognition, diagnosis, and behavioral treatment of persons with heart-focused anxiety.     

Oestrogen and progesterone do not regulate the expression of retinoic acid receptors and retinoid 'X' receptors in human endometrial stromal cells in vitro

Elucidation of the gene structure for retinoic acid receptor-(RAR-) has suggested a potential role for oestrogen in regulatingthe expression of RAR-. We have previously shown that all threeRAR types are expressed in human endometrial stromal cells invitro and that RAR- expression is induced in response to retinoicacid. The aim of this study was to ask whether oestradiol andprogesterone could play a part in regulating the expressionof RARs in human endometrial stromal cells and to establishthe patterns of expression of a related group of nuclear retinoidreceptors, retinoid ‘X’ receptors (RXRs) and theirpotential for regulation by steroid hormones. The RAR expressionpatterns of endometrial stromal cells, grown in steroid-freemedium, did not change in response to the presence of steroidhormones. Furthermore, the retinoic acid-mediated inductionof RAR- was not affected by oestradiol or progesterone, andwas dependent on the continued presence of retinoic acid. Ofthe three RXR types, only RXR- was detectably expressed in stromalcells in vitro and the expression of RXR- did not change inresponse to steroid hormones or retinoic acid. These data indicatethat oestradiol and progesterone are not important in the regulationof RAR and RXR expression in human endometrial stromal cells.     

Visceral leishmaniasis in the acquired immunodeficiency syndrome: Report of two cases

Core biopsies of the bone marrow are indispensable in the evaluation of fever of unknown etiology in human immunodeficiency virus-positive patients. We report two patients in whom visceral leishmaniasis was diagnosed based on the typical morphology, staining characteristics, and ultrastructure of the organisms.     

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.