Quantitative autoradiographic study of L-glutamate binding sites in normal and atrophic human cerebellum.

In the present work the distribution of L-glutamate binding sites in the different layers of human cerebellum of normal individuals and of seven patients who died with olivopontocerebellar atrophy (OPCA) was examined with the technique of quantitative autoradiography. Specific L-[3H]glutamate binding was higher in the molecular than in the granule cell layer of normal cerebellar tissue. A significant decrease of L-[3H]glutamate specific binding was observed in the molecular layer of all OPCA tissues. In the granule cell layer L-[3H]glutamate binding was decreased only in two patients who suffered from late-onset sporadic OPCA and in one patient who suffered from a form of OPCA inherited in a dominant manner. Quisqualate-sensitive binding sites were the most abundant binding sites in the molecular layer of normal cerebella, whereas N-methyl-D-aspartic acid (NMDA)-sensitive binding sites were the most abundant type in the granule cell layer. A significant decrease of quisqualate-sensitive and an increase in NMDA-sensitive binding sites were observed in the molecular layer of OPCA cerebellar tissues. No significant changes were observed in the granule cell layer of these tissues.     

Dopamine receptor and transporter levels are altered in the brain of Purkinje Cell Degeneration mutant mice

The Purkinje Cell Degeneration (Nna1pcd, pcd) mutant mouse is mainly characterized by the complete, primary loss of the Purkinje cells and the secondary, partial, retrograde loss of the granule and inferior olive neurons and is considered a model of human degenerative ataxia. We determined, by in vitro quantitative autoradiography and in situ hybridization, the effects of the Purkinje cell deprivation on the dopaminergic system of the Nna1pcd mutant mouse. The dopamine transporters, as determined by [3H]WIN35428 binding, were increased compared with wild-type mice in the ventral mesencephalic dopaminergic nuclei and in the lateral striatum, motor cortex and septum. In the cerebellum of Nna1pcd mice, the dopamine transporters showed a significant increase in the deep cerebellar nuclei, but were significantly decreased in the molecular layer. The D1-like receptors, as determined by [3H]SCH23390 binding, increased significantly in the Nna1pcd substantia nigra. The D2/D3 receptors, as determined by [3H]raclopride binding, exhibited a significant decrease in lateral divisions of the striatum. Significant increases in D2-like receptors, as determined by [3H]nemonapride binding, were observed in most divisions of the striatum as well as in septum, hippocampus, and piriform cortex. This D2-like fraction most probably corresponds to the D4 receptor subtype. In the cerebellum of Nna1pcd mice, D2-like receptors were significantly decreased in the molecular layer. The results suggest an increased excitatory input on the dopaminergic mesencephalic neurons and an alteration of the dopaminergic neurotransmission in basal ganglia, cortical and limbic regions of the Nna1pcd mutant mouse. In the cerebellum, the significant downregulation of the dopamine transporters and D2-like receptors in the mutant cerebellar molecular layer is possibly due to the absence of the Purkinje cells.     

Effects of Three Different Family-Based Interventions in Overweight and Obese Children: The “4 Your Family” Randomized Controlled Trial

Childhood overweight and obesity prevalence has risen dramatically in the past decades, and family-based interventions may be an effective method to improve children’s eating behaviors. This study aimed to evaluate the effectiveness of three different family-based interventions: group-based, individual-based, or by website approach. Parents and school aged overweight or obese children, 8–12 years of age, were eligible for the study. A total of 115 children were randomly allocated in one of the three interventions, and 91 completed the study (79% compliance); Group 1 (n = 36) received group-based interventions by various experts; Group 2 (n = 30) had interpersonal family meetings with a dietitian; and Group 3 (n = 25) received training through a specifically developed website. Anthropometric, dietary, physical activity, and screen time outcomes were measured at baseline and at the end of the study. Within-group comparisons indicated significant improvement in body weight, body mass index (BMI)-z-score, physical activity, and screen time from baseline in all three study groups (p < 0.05). Furthermore, total body fat percentage (%TBF) was also decreased in Groups 2 and 3. Between-group differences varied with body weight and %TBF change, being larger in Group 3 compared to Groups 1 and 2, in contrast to BMI-z-score, screen time, and health behaviors, which were significantly larger in Group 2 than the other two groups. In conclusion, personalized family-based interventions are recommended to successfully improve children’s lifestyle and body weight status.     

Immunolocalization of transitional cell carcinoma of the bladder with intravesically administered technetium-99m labelled HMFG1 monoclonal antibody

The aim of this study was the immunolocalization of transitional cell carcinoma of the bladder with a radiolabelled murine tumour-associated monoclonal antibody and the measurement of the absolute uptake of the antibody by the tumour. Fourteen patients with transitional cell carcinoma of the bladder received 3–6 mCi (111–222 MBq) of technetium-99m labelled HMFG1 monoclonal antibody intravesically and one patient, 2 mCi (74 MBq) of iodine-131 labelled 11.4.1, which is a non-tumour-specific monoclonal antibody. Four of the 15 patients were evaluated with singlephoton emission tomography (SPET) 1 1/2 to 2 h post administration. All patients underwent transurethral resection of the bladder tumour within 12–20 h following intravesical administration of the radiolabelled antibody. The radioactivity of biopsy specimens from normal urothelium and tumour areas were counted in a gamma counter. The mean uptake of the radiolabelled antibodies from normal and tumour sites was expressed as a percentage of the administered dose per kilogram of tissue. Conventional histology and immunohistochemistry using HMFGI monoclonal antibody were performed on paraffin sections of the biopsy specimens. Although our results are preliminary, it can be concluded that: (a) bladder tumours are well imaged by SPET when using^99mTc-HMFG1; (b) intravesically administered radiolabelled antibody remains on the bladder tissue and does not escape into the systemic circulation; (c) the wide range of tumour uptake values (0%–9.3% administered dose/kg) observed probably can be attributed to heterogeneity of the antigenic expression of the tumour; (d) values of^99mTc-HMFGI monoclonal antibody uptake by the tumour do not justify future attempts at radioimmunotherapy.     

Cystoid macular edema in a patient with acquired immunodeficiency syndrome and past ocular history of cytomegalovirus retinitis after initiation of protease inhibitors

Purpose: To describe a patient with acquired immunodeficiency syndrome (AIDS) who presented with cystoid macular edema (CME) which was not associated with active cytomegalovirus (CMV) retinitis or AIDS-related microvasculopathy. Method: A 32-year-old man with AIDS and a past ocular history of inactive CMV retinitis was placed on protease inhibitors when his CD4⁺ T lymphocyte counts dropped to 8 cells/mm³. Three months later, after his CD4⁺ T lymphocyte counts had increased to 196 cells/mm³ he complained of micropsia and metamorphopsia in his right eye of 1 week duration. The patient had a complete ocular examination including fluorescein angiography (FA). Results: Visual acuity (VA) was 7/10 OD. Fundus examination revealed CME and inactive CMV retinitis, and FA demonstrated CME and a hot disc. Two transseptal injections of corticosteroids were administered 2 weeks apart in the right eye as treatment of the CME. The patient reported gradual visual improvement and 6 weeks later, his VA was 10/10^-2. CME had resolved clinically and angiographically. Conclusions: CME in our case is associated with inactive CMV retinitis and gradually increasing number of CD4⁺ T lymphocytes after initiation of treatment with protease inhibitors. It may be amenable to regional administration of corticosteroids without reactivation of retinitis. This revised version was published online in July 2006 with corrections to the Cover Date.     

Relation Between Chronic Obstructive Pulmonary Disease and Antibiotics

Chronic obstructive pulmonary disease (COPD) constitutes a major health problem. Recurrent acute exacerbations are characteristic of the course of COPD (AECOPD) associated with significant healthcare costs and contribute to the progress of the disease. Given that almost half of AECOPD is caused by bacteria, administration of antibacterial agents is recommended for patients with severe exacerbations or severe underlying COPD. Optimal antibiotic selection for exacerbations has therefore incorporated quantifying the risk for a poor outcome of the exacerbation and choosing antibiotics differently for low risk and high risk patients. It is unclear whether antibiotics should be provided as prophylactic agents in COPD patients although ongoing trials are reexamining the question of whether the antiinflammatory action of antibiotics such as macrolides can be useful in preventing exacerbations. In addition, nowadays, the occurrence of pneumonia in COPD has received considerable recent attention as it appears to be increased by the use of inhaled corticosteroids.     

A somatic mutation in the thyrotropin receptor gene in a patient with an autonomous nodule within a multinodular goiter

Thyrotropin (TSH) is the prime regulator of thyroid cell growth and function and acts through the thyrotropin receptor (TSHR) located on the surface membrane of thyrocytes. Somatic heterozygous mutations that cause TSHR activation in the absence of TSH have been found in toxic adenomas and in hot nodules of multinodular goiters. Clinically and histologically heterogeneous nodules can share common gain-of-function mutations. Mutation prevalence varies greatly and is inversely related to iodine intake of the population. We report a Greek patient presenting with subclinical hyperthyroidism due to a fast-growing autonomous hyperplastic nodule in a long-standing multinodular goiter. Direct DNA sequencing showed that the hot nodule harbored a somatic heterozygous activating TSHR mutation: substitution of glutamine for leucine in the third transmembrane helix. This mutation (L512Q) was recently described in two solitary toxic adenomas. This report expands the spectrum of mutations shared by dissimilar hot nodules, supporting a common mechanism for nonautoimmune thyroid autonomy. The identification of the L512Q substitution demonstrates that gain-of-function TSHR mutations are encountered in Greece, although iodine deficiency has been significantly corrected over the last three decades.     

Cranial and postcranial skeletal variations induced in mouse embryos by mobile phone radiation

This study focuses on foetal development following mild daily exposure of pregnant mice to near field electromagnetic radiation emitted by a mobile phone. The investigation was motivated by the fact that the potentially hazardous electromagnetic radiation emitted by mobile phones is currently of tremendous public interest. Physically comparable pregnant mice were exposed to radiofrequency radiation GSM 900 MHz emitted by a mobile phone. Within 5 h after birth most cubs were fixed followed by double staining in toto, and conventional paraffin histology. Other cubs remained with their mothers until teeth eruption. Structural development was assessed by examining newborns for the presence of anomalies and/or variations in soft tissues and skeletal anatomy. Electromagnetic radiofrequency exposed newborns, externally examined, displayed a normal phenotype. Histochemical and histological studies, however, revealed variations in the exposed foetuses with respect to control ones concerning the ossification of cranial bones and thoracic cage ribs, as well as displacement of Meckelian cartilage. Littermates examined after teeth eruption displayed normal phenotypes. It is concluded that mild exposure to mobile phone radiation may affect, although transiently, mouse foetal development at the ossification level. The developmental variations observed could be explained by considering the different embryonic origin and mode of ossification of the affected skeletal elements.