Glial cell line-derived neurotrophic factor (GDNF) gene expression in the human brain: A post mortem in situ hybridization study with special reference to Parkinson's disease

Summary Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor for dopaminergic neurons. Since dopaminergic neurons degenerate in Parkinson's disease, this factor is a potential therapeutical tool that may save dopaminergic neurons during the pathological process. Moreover, a reduced GDNF expression may be involved in the pathophysiology of the disease. In this study, we tested whether altered GDNF production may participate in the mechanism of cell death in this disease. GDNF gene expression was analyzed by in situ hybridization using riboprobes corresponding to a sequence of the exon 2 human GDNF gene. Experiments were performed on tissue sections of the mesencephalon and the striatum from 8 patients with Parkinson's disease and 6 control subjects matched for age at death and for post mortem delay. No labelling was observed in either group of patients. This absence of detectable expression could not be attributed to methodological problems as a positive staining was observed using the same probes for sections of astroglioma biopsies from human adults and for sections of a newborn infant brain obtained at post-mortem. These data suggest that GDNF is probably expressed at a very low level in the adult human brain and its involvement in the pathophysiology of Parkinson's disease remains to be demonstrated. GDNF may represent a powerful new therapeutic agent for Parkinson's disease, however.     

Expression of the beta-nerve growth factor gene in male sex organs of the mouse, rat, and guinea pig.

Steady-state nerve growth factor (NGF) mRNA levels were estimated in male sex organs of the mouse, rat, and guinea pig by RNA blot hybridization analysis. The abundance of NGF mRNAs was in the order vas deferens greater than epididymis greater than or equal to seminal vesicles much greater than testis. NGF mRNA levels in these organs were compared with those estimated for other rat peripheral tissues and were found to correlate with the density of their sympathetic innervation, with the exception of guinea pig prostate. Castration had no significant effect on NGF mRNA levels in the guinea pig prostate, suggesting that NGF synthesis in this tissue is not under direct androgen control. NGF-like and proNGF-like immunoreactivities were localized by immunohistochemical techniques in the secretory cells of the glandular epithelium of the guinea pig prostate and in germ cells in the seminiferous tubules of the mouse testis.     

Thalamo-peduncular germinoma]

A 24 year-old patient presented with chronic intracranial hypertension, palsy of both abducens nerves and upward gaze, and right hypoesthesia. CT scan and MRI showed a left thalamic tumor infiltrating the left cerebral peduncle. A stereotactic biopsy revealed a germ cell tumor. Following radiotherapy the patient recovered except for ophthalmoplegia. The tumor totally disappeared on CT scan and MRI.     

Different clinical types of degenerative aphasia

The authors report 3 cases of slowly progressive aphasia with different language disturbances: anomia, pure word deafness and Broca's aphasia. All patients were independent in daily life activities. Insight, judgement and overall behaviour were intact. There was no major disturbance of other cognitive functions, but psychometric tests showed mild deficits suggesting widespread involvement. CT scans and magnetic resonance imaging showed focal dilatation of the left sylvian fissure. A positron emission tomographic study showed left perisylvian hypometabolism. A review of the literature yielded an increasing number of cases of this degenerative syndrome affecting dominant hemisphere language areas. Our cases confirm the clinical heterogeneity of degenerative aphasia. Postmortem neuropathological examinations are rare and many causes are found: Pick's disease, Alzheimer's disease or aspecific gliosis.     

Long-term hypertransaminasemia disclosing a muscular disease

Prolonged increase in serum transaminase activity is usually seen in chronic liver disease. Evaluation in one patient with such a prolonged increase having no evidence of liver disease including histological examination, revealed a limb girdle muscular dystrophy. This case suggests that a muscular disease should be suspected in all children with persistent increase in serum transaminase activity when the liver is apparently normal.     

Evaluation of the end-expiratory lung volume as an indirect index of bronchial constriction in asthma

The purpose of this study was to evaluate the merits of the end expiratory lung volume as an indirect ventilatory index of bronchial obstruction and to show an application of continuous monitoring of lung volume in asthmatic patients. The accuracy of the external measurements (IS) of functional residual capacity (FRC) was controlled by comparing them with the helium measurements (DS) obtained during nine methacholine tests (IS = 0.06 + 1.065 DS in litres: R2 = 0.99). Seven asthmatics (18-48 yr) were monitored by measuring rib cage and abdominal perimeter variations. This was done in basal condition, after methacholine-induced bronchoconstriction and after bronchodilation by either salbutamol or oxytropium bromide inhalation. All the subjects were investigated on two separate days and were their own control. Bronchoconstriction produced a significant increase (p less than 0.01) of tidal volume (VT: + 67%), external minute ventilation (VE: + 58%), mean inspiratory flow (VT/TI: + 78%) and FRC (+ 26.5%) while frequency (f) and fractional inspiratory time (TI/TT) fluctuated non significantly. In the group of seven tested subjects, there was a significant correlation (p less than 0.01) between forced expiratory volume in one second (FEV1) and VE, FEV1 and VT/TI, FEV1 and FRC. However, the individual regression line showed a significant relationship only between FEV1 and FRC (R2 = 0.80 +/- 0.04). We therefore conclude that the variation of the end expiratory level can be chosen as an indirect index of bronchoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Value and limits of "critical auscultation" of neck bruits

Within a group of 2,000 patients evaluated, most of them with symptoms of cerebrovascular insufficiency, 441 had a monolateral or bilateral cervical bruit. The 627 sides with an audible bruit were divided into main groups (A) symptomatic (TIA and/or stroke homolateral to the bruit), (B) possibly symptomatic (non-side-related symptoms), (C) asymptomatic (C1, in totally asymptomatic patients; C2, in patients with symptoms dependent on the hemisphere contralateral to the cervical bruit). Each patient was studied by means of clinical (history, blood pressure in both upper limbs, phonoendoscopic auscultation at various levels) and noninvasive instrumental examinations (CW Doppler spectrum analysis). An apparently primitive cervical bruit corresponded to a lesion of the carotid bifurcation in 61% of the cases (positive predictive value) whereas a normal bifurcation was detected in 70% of the cases in which the cervical bruit was considered as secondary (negative predictive value); the diagnostic accuracy of the "critical auscultation" has a value therefore of 63%, with a sensitivity of 84% and a specificity of 40%. The results obtained in the different groups of patients (symptomatic or asymptomatic) were not significantly different (chi-square). Even though maintaining the value of a cervical bruit as a sign of carotid stenosis or occlusion and consequently confirming the importance of neck auscultation, the authors conclude that the critical auscultation as commonly performed is not capable of excluding the presence of a carotid lesion with sufficient reliability, even in totally asymptomatic patients.