QSPR models to predict the physical hazards of mixtures: a state of art.

Physical hazards of chemical mixtures, associated for example with their fire or explosion risks, are generally characterized using experimental tools. These tests can be expensive, complex, long to perform and even dangerous for operators. Therefore, for several years and especially with the implementation of the REACH regulation, predictive methods like quantitative structure-property relationships have been encouraged as alternatives tests to determine (eco)toxicological but also physical hazards of chemical substances. Initially, these approaches were intended for pure products, by considering a molecular similarity principle. However, additional to those for pure products, QSPR models for mixtures recently appeared and represent an increasing field of research. This study proposes a state of the art of existing QSPR models specifically dedicated to the prediction of the physical hazards of mixtures. Identified models have been analysed on the key elements of model development (experimental data and fields of application, descriptors used, development and validation methods). It draws up an overview of the potential and limitations of current models as well as areas of progress towards enlarged deployment as a complement to experimental characterizations, for example in the search for safer substances (according to safety-by-design concepts).

Somatosensory evoked potentials in the assessment of peripheral neuropathies: Commented results of a survey among French-speaking practitioners and recommendations for practice.

BACKGROUND: Somatosensory evoked potentials (SSEPs) are increasingly performed for the assessment of peripheral neuropathies, but no practical guidelines have yet been established in this specific application. STUDY AIM: To determine the relevant indication criteria and optimal technical parameters for SSEP recording in peripheral neuropathy investigation. METHODS: A survey was conducted among the French-speaking practitioners with experience of SSEP recording in the context of peripheral neuropathies. The results of the survey were analyzed and discussed to provide recommendations for practice. RESULTS: SSEPs appear to be a second-line test when electroneuromyographic investigation is not sufficiently conclusive, providing complementary and valuable information on central and proximal peripheral conduction in the somatosensory pathways. CONCLUSIONS: Guidelines for a standardized recording protocol, including the various parameters to be measured, are proposed. CLINICAL RELEVANCE: We hope that these proposals will help to recognize the value of this technique in peripheral neuropathy assessment in clinical practice.

QSPR prediction of physico-chemical properties for REACH.

For registration of a chemical, European Union REACH legislation requires information on the relevant physico-chemical properties of the chemical. Predicted property values can be used when the predictions can be shown to be valid and adequate. The relevant physico-chemical properties that are amenable to prediction are: melting/freezing point, boiling point, relative density, vapour pressure, surface tension, water solubility, n-octanol-water partition coefficient, flash point, flammability, explosive properties, self-ignition temperature, adsorption/desorption, dissociation constant, viscosity, and air-water partition coefficient (Henry's law constant). Published quantitative structure-property relationship (QSPR) methods for all of these properties are discussed, together with relevant property prediction software, as an aid for those wishing to use predicted property values in submissions to the European Chemicals Agency (ECHA).

Muscle strength and body composition in adult women with Marfan syndrome.

OBJECTIVE: The purpose of this study was to assess skeletal muscle function and body composition in a group of women with Marfan syndrome compared with matched controls. METHODS: The 21 women who were receiving follow-up for Marfan syndrome at our institution, were free of major cardiovascular disease, and consented to the study performed isokinetic and isometric knee extension and flexion maximal strength tests and had their body composition evaluated using dual-energy X-ray absorptiometry (DEXA). The same assessments were done in 19 matched controls. RESULTS: A significant decrease in lean leg mass with no change in total soft-tissue leg mass was noted in the patients compared with the controls. Peak torque values for the quadriceps and hamstring muscle groups were decreased in the patients, but only quadriceps strength was significantly reduced after normalization for lean leg mass. CONCLUSION: The muscle strength reduction in Marfan patients was not fully explained by a decrease in lean leg mass, suggesting qualitative skeletal-muscle alterations related to abnormal fibrillin expression in muscle connective tissue.

Exacerbation of sleep-apnoea related nocturnal blood-pressure fluctuations in hypertensive subjects.

Obstructive sleep apnoea syndrome (OSAS) induces marked haemodynamic fluctuations during sleep that might be deleterious to the cardiovascular system. The influence of daytime blood pressure (BP) levels and aging on short-term BP variability during sleep in OSAS patients was investigated. Twenty-nine subjects with newly-diagnosed untreated OSAS were categorised into three groups: normotensive subjects aged <50 yrs (n=10); subjects aged <50 yrs with untreated hypertension (n=8); and normotensive subjects aged >50 yrs (n=11). Beat-by-beat BP was recorded with a Finapres device during polysomnography. The average values+/-SD of apnoea-related BP elevations and the values of the frequency distribution of all BP variations during sleep were assessed to estimate short-term BP variability. Apnoea-related systolic (or diastolic) BP elevations were significantly greater in hypertensives than in normotensives aged <50 yrs (50.3+/-4.88 versus 30.7+/-2.14 mmHg, p<0.001), as was the SD of systolic (or diastolic) BP variations during sleep (19.6+/-2.22 versus 11.1+/-0.73, p<0.001). Short-term BP variability was not significantly increased in normotensive elderly patients. To conclude, the results suggested that systemic hypertension is associated with a greater exacerbation of short-term variability during sleep in obstructive sleep apnoea syndrome patients.

Isolation of a normal human thyroid cell line: hormonal requirement for thyroglobulin regulation.

The long-term culture of functional follicular cells from normal adult human thyroid tissue has been obtained. They were expanded using a 1:2 split ratio until passage 28 (present status) in Click-RPMI medium enhanced with 5% fetal calf serum and diverse associations of hormones or components including porcine insulin and bovine thyrotropin. At passages 10 and 20, chromosome countings showed a normal diploid number and a normal karyotype. In calf serum containing media, cells are epithelial in the presence of thyrotropin (TSH) but present a slight elongated form in the absence of TSH. In serum-free media, 30 minutes after TSH stimulation, both epithelial and elongated cells changed in morphology to stellate-shaped, arborized forms, indicating the presence of functional TSH-receptors even in long term (18 months) TSH-free cultures. Cells produce thyroglobulin constitutively and large amounts of thyroglobulin are easily recovered in TSH-supplemented media, especially in the presence of insulin. Thyroglobulin production was increased versus days under TSH or insulin stimulation. Combination of the two hormones clearly resulted in a synergistic and not an additive effect. The other hormones present in the 6H components (transferrin, glycylhistidyl-lysine, somatostatin, and hydrocortisone) had no positive effect on thyroglobulin accumulation in media in our experimental conditions. Addition of TSH to hormone-free cultures or to insulin-, insulin plus hydrocortisone-, or 5H-containing cultures resulted in a clear increase in thyroglobulin production. Withdrawal of TSH from 6H cultures resulted in a decrease in thyroglobulin accumulation in media. Six months were required to select fibroblast-free cultures and to get passage 6. But only 17 months separated passage 6 to passage 28, indicating that the proliferative rate is increasing with in vitro cell adaptation. Such normal adult thyroid cells, thyroglobulin-producing, TSH, and insulin-sensitive, represent a new normal human thyroid cell line allowing comparative studies with cells originating from pathologic thyroid tissues.

Simple, reliable and fast spectrofluorometric method for determination of plasma Verteporfin (Visudyne) levels during photodynamic therapy for choroidal neovascularization.

Photodynamic therapy with Verteporfin, a potent photosensitizer dye, is a very effective treatment for age related macular degeneration due to choroidal neovascularization. Photodynamic therapy offers the potential for selective tissue injury in part attributable to preferential localization of Verteporfin, administrated by intravenous infusion, to the choroidal neovascularization complex and irradiation of the complex with non-laser thermal light at 690 nm resulting in at least temporary thrombosis and vessel closure. Verteporfin is a benzoporphyrin derivative monoacid ring A formulated as a unilamellar liposome. In the blood Verteporfin is associated with lipoprotein fractions and is rapidly cleared via a receptor-mediated uptake mechanism due the high expression of LDL receptors in neovascular tissues. Verteporfin was undetectable in plasma 24 hr after infusion of the recommended dose: 6 mg/m2 of body surface area. The main side effect is photosensitivity of skin which is usually short-lived (24-48 hr) with a low incidence (2.3%). As skin photosensitivity depends on circulating rather than tissue drug levels, we investigate the possibility of developing a simple, fast and reliable spectrofluorometric method to measure plasma Verteporfin levels. Fluorescence emission spectrum (550-750 nm) of 1:10 saline diluted plasma with lambda exc=430 nm showed a characteristic emission peak at 692 nm, the height being proportional to the Verteporfin levels. The sensitivity is around 100 ng/ml and the pharmacokinetics of Verteporfin has been studied from 0 to 5 hr after infusion in six patients older than 65 years with age-related macular degeneration.

Protection of puppies against canine herpesvirus by vaccination of the dams.

Six bitches free of canine herpesvirus 1 (CHV-1) were vaccinated against the virus; a first injection was given 10 days after the presumed date of mating and a second six weeks later. Six similar bitches were left unvaccinated as controls, and all the pups were challenged oronasally with a virulent strain of CHV-1 at three days of age. All the vaccinated bitches seroconverted and had high antibody titres when the puppies were challenged, but the control bitches remained seronegative. In the control group, 62 per cent (18 of 29) of the pups died of CHV-1-induced disease; most of them showed typical clinical signs and macroscopic lesions, and CHV-1 infection was confirmed by the isolation of the virus or by PCR. None of the puppies in the vaccinated group died of CHV-1 infection. The efficacy of the vaccine was confirmed in CHV-1-positive breeding units. The rate of pregnancy tended to be higher in vaccinated bitches and the mortality of pups before weaning was significantly reduced in the litters born to vaccinated bitches.

Age-related morphological changes of the deltoid muscle from 50 to 79 years of age.

A quantitative analysis of deltoid muscle biopsy specimens was performed by light microscopy in 26 males and 25 females aged 50-79 years without known neuromuscular disease. Muscle fibre size, fibre type distribution and increase in mitochondrial content in muscle fibres were examined using a semi-automatic image analysis system. This study showed significant age- and gender-related differences. In females, there was marked atrophy of type II fibres with increasing age, specially of type IIb fibres, but no significant change in muscle fibre type distribution. In males, there was diminution in the relative proportion of type IIb fibres with increasing age but no significant muscle fibre atrophy. Mitochondrial aggregates increased with age, and this increase was observed earlier in females than in males. The gender-related morphological changes observed in the present study differ somewhat from those reported in the literature. The differences between males and females may be partially related to gender differences in muscular activity and may reflect an earlier decline in deltoid muscle strength in females. The existence of these age and gender changes should be taken into account in the interpretation of muscle biopsies of aged individuals.

Mitochondrial DNA transfer RNA gene sequence variations in patients with mitochondrial disorders.

Many different pathogenic mutations in the mitochondrial (mt) transfer RNA (tRNA) genes have been reported for patients with mitochondrial encephalomyopathy. Although some of them are recurrent, most have only been described once and appear to be restricted to one patient or to one family. The incidence of mt tRNA gene alterations is not known, even though the frequency of some recurrent mutations has been analysed both in patients and in the general population. In this study, we describe the results of stepwise screening for sequence variations in the mt tRNA genes of 166 patients selected according to several criteria. Extensive sequence analysis of the tRNA genes was performed using denaturing gradient gel electrophoresis. A total of 31 patients (19%) were found to harbour significant levels of a pathogenic mutation, thus confirming the importance of mt tRNA mutations in human pathology. Forty-three different sequence variations were found, illustrating the great diversity of the mtDNA sequence in humans. The functional assessment of all these sequence variations represented a difficult task; it was mostly based on indirect data, such as the phylogenetic conservation of modified nucleotides and the proportions of variant species in different tissues of the index case or in blood of maternal relatives. Direct demonstration of a correlation between the proportion of heteroplasmic sequence variations and the cytochrome c oxidase defect was performed at the single muscle-fibre level. Eleven heteroplasmic sequence variations were found, six of which are new mutations. One is a known Caucasian polymorphism but the other 10 are pathogenic. Two of them are the well-known pathogenic MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) (A3243G) and MERRF (myoclonic epilepsy with ragged-red fibres) (A8344G) point mutations. They were found in 23 patients. The eight other mutations were restricted to one patient. The pathogenic nature of these mutations was demonstrated directly for five of them and hypothesized from indirect arguments for the other three. Thirty-two homoplasmic sequence variations were found. Twenty-nine were considered to be polymorphisms, even though 15 of these were found for the first time in our patients and two others had been reported previously as pathogenic. The pathogenic nature of three homoplasmic variants remains questionable.

Glut-1 translocation in FRTL-5 thyroid cells: role of phosphatidylinositol 3-kinase and N-glycosylation.

It was previously demonstrated that insulin or TSH treatment of FRTL-5 cells resulted in an elevation of glucose transport and in an increase of cell surface expression of the glucose transporter Glut-1. However, the signaling mechanisms leading to the insulin or TSH-induced increase in the cell surface expression of Glut-1 were not investigated. In the present study, we demonstrated that wortmannin and LY294002, two specific inhibitors of phosphatidylinositol 3-kinase (PI3-kinase), interfere both in the signaling pathways of insulin and TSH leading to glucose consumption enhancement and Glut-1 translocation. Two hours after insulin treatment, TSH or cAMP analog (Bu)2cAMP stimulation, glucose transport was increased and most of the intracellular Glut-1 pool was translocated to plasma membranes. Wortmannin or LY294002 blocked the insulin, (Bu)2cAMP, and the TSH-induced translocation of Glut-1. Wortmannin or LY294002 alone did not alter the basal ratio between intracellular and cell surface Glut-1 molecules. These results suggest that in FRTL-5 cells wortmannin and LY294002 inhibited the insulin, (Bu)2cAMP and TSH events leading to Glut-1 translocation from an intracellular compartment to the plasma membrane. Likewise, (Bu)2cAMP effects on glucose transport and Glut-1 translocation to plasma membrane were repressed by PI3-kinase inhibitors but not by the protein kinase A (PKA) inhibitor H89. We suggest that (Bu)2cAMP stimulates Glut-1 translocation to plasma membrane through PI3-kinase-dependent and PKA-independent signaling pathways. To further elucidate mechanisms that regulate the translocation of Glut-1 to cell membrane, we extended this study to the role played by the N-glycosylation in the translocation and in the biological activity of Glut-1 in FRTL-5 cells. For this purpose we used tunicamycin, an inhibitor of the N-glycosylation. Our experiments with tunicamycin clearly showed that both the glycosylated and unglycosylated forms of the transporter reached the cell surface. Likewise, a decrease in glucose consumption (-50%) after treatment of cells with tunicamycin was accompanied by a decrease (-70% vs. control) in the membrane expression of a 50-kDa form of Glut-1 and an increase in its unglycosylated 41-kDa form. These results suggest that carbohydrate moiety is essential for the biological activity of glucose transport but is not required for the translocation of Glut-1 from the intracellular membrane pool to the plasma membrane.

Hexamethylene bisacetamide (HMBA) increases thyroglobulin levels in porcine thyroid cells without increasing cyclic-AMP.

The polar planar compound hexamethylene bisacetamide (HMBA) is an inducer of terminal differentiation which has been extensively studied in the murine erythroleukemia cells (MELC). We have tested this compound in normal porcine thyroid cells in primary culture where it either activates or inhibits the major tissue specific functions of these cells: it induces the reorganization of cells into follicles, prevents the loss of thyrotropin sensitivity in monolayer cells, activates cell growth but inhibits their iodide metabolism. In this paper, we demonstrate that HMBA acts on the total thyroglobulin levels measured in cell layers plus media. This specific marker of thyroid tissue is increased by HMBA both in kinetics and in concentration-response experiments. HMBA per se does not increase the total cyclic AMP measured either during the first hours after stimulation or in the following days when compared to controls. As expected, cyclic AMP in the same experiment increased rapidly within minutes after the cells were challenged by TSH (positive control). Altogether, the results show that the drug HMBA mimics thyrotropin effects on thyroglobulin levels measured in porcine thyroid cells in culture. This modulation cannot be explained by an increase in cyclic AMP, indicating that despite similarities between TSH and HMBA effects, the mechanism of the mode of action of these two molecules is very different.

Hexamethylenebisacetamide modulation of thyroglobulin and protein levels in thyroid cells is not mediated by phosphatidylinositol-3-kinase: a study with wortmannin.

Hexamethylenebisacetamide (HMBA) induces in murine erythroleukemia cells (MELC) the commitment to terminal differentiation leading to globin gene expression. In the thyroid, HMBA acts as a growth factor and also as a differentiating agent. In the present paper, we studied the effect of HMBA on the very specific thyroid marker thyroglobulin (Tg) in two different thyroid cell systems, i.e., porcine cells in primary culture and ovine cells in long term culture. Using wortmannin, a specific inhibitor of phosphatidylinositol-3-kinase, we investigated whether this enzyme is involved in HMBA mode of action. We found that HMBA is a positive modulator of Tg production in porcine cells, but a negative effector in the OVNIS cell line. As all HMBA effects studied in the present paper, i.e., Tg production and total protein levels, are not inhibited by wortmannin, we suggest the non-involvement of phosphatidylinositol-3-kinase in HMBA mode of action.

DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid) increases iodide trapping, inhibits thyroperoxidase and antagonizes the TSH-induced apical iodide efflux in porcine thyroid cells.

4,4'-Di-isothiocyanatostilbene-2,2'-disulfonic acid (DIDS), an inhibitor of several anionic channels and transporters including the band 3 protein of the red blood cell membrane was tested on iodide metabolism in cultured porcine thyroid cells. We used three experimental cell culture models: (i) forskolin-stimulated correctly inside-in polarized follicle-associated thyroid cells cultured onto plastic support (ii) suspensions of isolated cells derived from such cultures (iii) polarized monolayers in bicameral chambers. DIDS was observed to increase free-iodide trapping in all conditions. Organification of iodide by follicle-associated cell cultures incubated for 6 h decreased as a function of DIDS concentration with an IC50 of 5 x 10(-5) M. This block in organification is accounted for a block in thyroperoxidase activity as in vitro both purified lactoperoxidase and purified porcine thyroperoxidase were inhibited by DIDS with a similar dose-dependency the IC50 being also of 5 x 10(-5) M. Both control and DIDS-treated cells in suspension, actively trapped iodide and reached a steady concentration in about 50 min; however the plateau was 4.4-fold higher in (10(-3) M) DIDS-treated cells. Acute TSH-stimulation at this plateau of 125I-preloaded cells in suspension in the presence of 2 mM methimazole (MMI) induced a fast release of iodide from these cells as expected (first step of the TSH-biphasic effect). This TSH-induced iodide efflux was however completely inhibited by DIDS (10(-3) M). Furthermore, addition of DIDS to the apical compartment of TSH-prestimulated cell monolayers in bicameral chambers resulted in an increase in intracellular-iodide concentration and in an inhibition of iodide efflux into the apical medium. Taken together, the present results demonstrate that DIDS mainly interacts with two main components of the thyroid apical cell membrane: thyroperoxidase and a cAMP-sensitive iodide channel.

Usefulness of neurogenic motor evoked potentials for spinal cord monitoring: findings in 112 consecutive patients undergoing surgery for spinal deformity.

Neurogenic motor evoked potential (NMEP) monitoring, which basically represents a monitoring of both motor and somatosensory tracts, has been proposed as a warning system in preventing neural damage during spinal surgery. The aim of this study was to report our clinical experience in 112 consecutive patients undergoing surgery for spinal deformity, and to emphasize the interest of NMEP monitoring. NMEPs were elicited in each patient by electrical stimulation of the spinal cord via needle electrodes placed by the surgeon in the rostral part of the surgical field, and recorded from the right and left sciatic nerves. Concomitantly, somatosensory evoked potentials (SSEPs) were obtained using a standard method. No false-negative cases of intra-operative spinal cord damage were reported. In 3 patients, both NMEPs and SSEPs suddenly disappeared during specific surgical manipulations of the vertebral implants. In these patients, the level of the lesion was easily recognized by moving the stimulating electrodes of NMEPs along the spinal cord, allowing the surgeon to perform laminectomy at the appropriate vertebral level. Spinal cord decompression was a success in two patients, the last unfortunately being paraplegic. Two additional patients exhibited transient reduction in NMEP amplitude at the insertion of a rod while SSEPs did not change significantly. In these two cases, the surgeon modified his procedure according to the NMEP changes, possibly avoiding a neurological complication. Each time evoked potentials were significantly altered, significant information was more rapidly acquired with NMEPs than with SSEPs. These results suggest that NMEPs can be used as primary choice for detecting impeding lesion of the spinal cord during critical steps of spinal surgery.

[Hexamethylene bisacetamide (HMBA) prevents the loss of porcine thyroid monolayer cells to thyrotropin sensitivity]. / L'hexaméthylène bisacétamide (HMBA) supprime la perte de sensibilité des cellules thyroïdiennes monocouches de porc à la thyrotropine.

The polar compound hexamethylenebisacetamide (HMBA) is a differentiating agent in the murine erythroleukemia cell system (MELC). It induces, like dimethylsulfoxide, the commitment to terminal differentiation leading to a recovery in the expression of several genes like the globin gene. This molecule which also induces differentiation in other cellular types is a growth agent for human, ovine and porcine thyroid cells. Forty-eight hours after the onset of culture, porcine thyroid monolayer cells do not respond to thyrotropin (TSH). We demonstrate that a pretreatment from the onset of culture with HMBA of porcine thyroid cells prevents the loss of TSH-sensitivity. The TSH-sensitivity is concentration-dependent in HMBA and leads to the reorganization of cells into follicles, even in the presence of HMBA. However, the withdrawal of HMBA when TSH is added is absolutely required to obtain a total recovery in iodide trapping and organification. If HMBA is present during TSH-stimulation, it inhibits iodide trapping partially but iodide organification completely Cells remain sensitive to TSH for at least 12 days if HMBA treated, and their sensitivity is totally restored after 3, 6 or 9 days of TSH-stimulation. HMBA, which is, like TSH, a growth agent for the thyroid cell and an agent that maintains some of the specialized functions, could be a putative candidate to obtain normal human thyroid cell lines.

Effects of isoflurane and desflurane on neurogenic motor- and somatosensory-evoked potential monitoring for scoliosis surgery.

BACKGROUND: Most techniques used to monitor spinal cord tracts are sensitive to the effects of anesthesia, particularly to volatile anesthetic agents. The aim of this prospective study was to show that evoked potentials recorded from the peripheral nerves after spinal cord stimulation, so-called neurogenic motor evoked potentials, are resistant to clinical concentrations of isoflurane or desflurane, compared with somatosensory-evoked potentials. METHODS: Twenty-three patients were studied during surgery to correct scoliosis. The background anesthetic consisted of a continuous infusion of propofol. Isoflurane (n = 12) or desflurane (n = 11) were then introduced to achieve 0.5 and 1.0 end-tidal minimum alveolar concentrations (MAC), both in 50% oxygen-nitrous oxide and in 100% oxygen. Somatosensory-evoked potentials were elicited and recorded using a standard method, defining cortical P40 and subcortical P29. Neurogenic motor-evoked potentials were elicited by electric stimulation of the spinal cord via needle electrodes placed by the surgeon in the rostral part of the surgical field. Responses were recorded from needle electrodes inserted in the right and left popliteal spaces close to the sciatic nerve. Stimulus intensity was adjusted to produce a supramaximal response; that is, an unchanged response in amplitude with subsequent increases in stimulus intensity. Measurements were obtained before introducing volatile agents and 20 min after obtaining a stable level of each concentration. RESULTS: Isoflurane and desflurane in both 50% oxygen-nitrous oxide and 100% oxygen were associated with a significant decrease in the amplitude and an increase in the latency of the cortical P40, whereas subcortical P29 latency did not vary significantly. Typical neurogenic motor-evoked potentials were obtained in all patients without volatile anesthetic agents, consisting of a biphasic wave, occurring 15 to 18 ms after stimulation, with an amplitude ranging from 1.3 to 4.1 microV. Latency or peak-to-peak amplitude of this wave was not significantly altered with isoflurane and desflurane, either in the presence or in the absence of nitrous oxide. CONCLUSIONS: Compared with cortical somatosensory-evoked potentials, neurogenic motor-evoked potential signals are well preserved in patients undergoing surgery to correct scoliosis under general anesthesia supplemented with isoflurane or desflurane in concentrations as great as 1 MAC.

Hexamethylenebisacetamide (HMBA) is a growth factor for human, ovine and porcine thyroid cells.

Hexamethylenebisacetamide (HMBA) provokes in murine erythroleukemia cells (MELC) a commitment to terminal differentiation leading to the activation of the expression of hemoglobin. HMBA has been tested also in other cells from colon cancer, melanoma or lung cancer. However it has not yet been tested in the thyroid. We demonstrate in this paper that HMBA in kinetics and concentration-response experiments increases the proliferation of human thyroid cells isolated from Graves'-Basedow patients. It also acts like a growth factor for ovine and porcine thyroid cells, respectively, from the OVNIS line and the ATHOS line. This molecule which is a differentiating factor in the MELC system and a growth factor in human thyroid cell cultures represents a potential to get human thyroid cell lines expressing specialized functions.

[Anarthria, progressive apraxia and extrapyramidal syndrome: an uncommon clinical form of corticobasal degeneration? A case studied by HMPAO Tc99m single-photon emission tomography]. / Anarthrie, apraxie progressive et syndrome extra-pyramidal: forme clinique particulière de dégénérescence cortico-basale? Un cas avec étude en tomographie par émission monophotonique au HMPAO Tc99M.

A 48-year-old man presented with impaired joint movement and buccofacial apraxia. The disease progressed for six years associating an akineto-hypertonic syndrome, marked anarthria, saliva incontinence, bi-opercular syndrome, bucco-facial apraxia, severe global gestual apraxia and a frontal syndrom. Oculo-motricity and gait were normal. Magnetic resonance imaging of the brain demonstrated fronto-parietal atrophy and HMPAO Tc99 tomography revealed hypoperfusion of the cortex clearly predominating in the left parietal region. These particular findings with predominantly intense joint involvement is similar to the clinical picture in corticobasal degeneration--subcortical signs (progressively uncontrollable hypertonia) together with cortical signs (severe gestual apraxia). The neuroradiological imaging and functional results also suggest a degenerative process.