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Biomedical subjects

C Pons

Publications and source records attributed to C Pons.

At least 19 recordsLinked to original sources

Measurement properties of the short version of the Van Lieshout test for arm/hand function of persons with tetraplegia after spinal cord injury.

STUDY DESIGN: Two validation studies. OBJECTIVES: To assess the measurement properties of the short version of the Van Lieshout test (VLT-SV), a new test for arm/hand function of persons with tetraplegia after spinal cord injury (SCI). SETTING: Two specialized rehabilitation centres in The Netherlands. METHODS: Study 1 (N=12)--assessment of inter-rater reliability (intraclass correlations (ICC); weighted kappa; Bland-Altman plots). Study 2 (N=55)--assessment of convergent validity by computing Spearman's correlations with the Grasp-Release test (GRT; criterion standard) and with motor level of injury, ASIA impairment scale, international classification for surgery of the hand, and the self-care and transfer scales of the functional independence measure. All statistics were computed separately for the right- and the left-hand scores. RESULTS: Inter-rater reliability was excellent (ICC 0.98 and 0.99). Agreement was independent of the height of the scores and the limits of agreement were +/-0.5 points on a 0-5 scale. Convergent validity was very good with a Spearman correlation of 0.87 and 0.90 between the VLT-SV and the GRT and correlations between 0.35 and 0.85 with the other indicators of arm/hand function. CONCLUSION: The VLT-SV seems a reliable and valid test to assess arm/hand function of persons with tetraplegia after SCI.

Activities of Daily Living↗

Earth pigments in painting: characterisation and differentiation by means of FTIR spectroscopy and SEM-EDS microanalysis.

Analytical characterisation of natural earths (ochres, siennas, umbers and green earths) has been carried out using Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) coupled to an energy dispersive X-Ray spectrometer (EDS). The study of these pigments, which are found in works of art, is very important since it can shed light on their source or the pictorial technique used. FTIR spectroscopy is suitable for the identification and differentiation of ochres and siennas. According to the matrix of the sample, FTIR allows the classification of ochres into ochres containing kaolinite and ochres containing sulphate. One of the goals of this research has been to establish a relationship between the matrix and the source of the samples tested. SEM-EDS is probably a better technique than FTIR for characterising umbers and green earths since they do not exhibit significant differences when FTIR studies are performed.

Journal Article↗

[Surgical removal of debilitating neurogenic heterotopic ossifications of the hip].

Two men, aged 24 and 52 years, developed neurogenic heterotopic ossifications of the hip, the first following a cervical spinal-cord injury and the second after prolonged artificial ventilation following bowel surgery. The stiffness caused problems when sitting and when performing general daily activities; the second patient who was ambulatory, also had problems walking. CT investigation clearly showed the localisation of the ossifications. After surgical removal of the ossifications both patients were able to sit for longer periods without low-back pain and the ambulatory function of the second patient was much improved. Indomethacin was given postoperatively and no recurrence of the ossification was seen. A number of per- and postoperative complications are associated with the surgical removal of neurogenic heterotopic ossifications of the hip. These include damage to surrounding structures and infection. However taking into account the improved range of movement and increased independence of the patient, it is a useful intervention for this debilitating condition.

Adult↗

Development of a citrus genome-wide EST collection and cDNA microarray as resources for genomic studies.

A functional genomics project has been initiated to approach the molecular characterization of the main biological and agronomical traits of citrus. As a key part of this project, a citrus EST collection has been generated from 25 cDNA libraries covering different tissues, developmental stages and stress conditions. The collection includes a total of 22,635 high-quality ESTs, grouped in 11,836 putative unigenes, which represent at least one third of the estimated number of genes in the citrus genome. Functional annotation of unigenes which have Arabidopsis orthologues (68% of all unigenes) revealed gene representation in every major functional category, suggesting that a genome-wide EST collection was obtained. A Citrus clementina Hort. ex Tan. cv. Clemenules genomic library, that will contribute to further characterization of relevant genes, has also been constructed. To initiate the analysis of citrus transcriptome, we have developed a cDNA microarray containing 12,672 probes corresponding to 6875 putative unigenes of the collection. Technical characterization of the microarray showed high intra- and inter-array reproducibility, as well as a good range of sensitivity. We have also validated gene expression data achieved with this microarray through an independent technique such as RNA gel blot analysis.

Citrus↗

Molecular pathology of endometrial hyperplasia and carcinoma.

Four different genetic abnormalities may occur in endometrioid adenocarcinomas of the endometrium (mircosatellite instability and mutations in the PTEN, k-RAS and beta-catenin genes), whereas nonendometrioid carcinomas of the endometrium often have p53 mutations and loss of heterozygosity on several chromosomes. Occasionally, a nonendometrioid carcinoma may develop as a result of dedifferentiation of a preexisting endometrioid carcinoma; in such a case, the tumor exhibits overlapping clinical, morphologic, immunohistochemical, and molecular features of the 2 types. The insaturation of microsatellite instability in endometrial carcinogenesis seems to occur late in the transition from complex hyperplasia to carcinoma, and it is preceded by progressive inactivation of MLH-1 by promoter hypermethylation. Moreover, the endometrioid adenocarcinomas that exhibit microsatellite instability show a stepwise progressive accumulation of secondary mutations in oncogenes and tumor suppressor genes that contain short-tandem repeats in their coding sequences. Mutations in the PTEN and k-RAS genes are also frequent in endometrioid adenocarcinomas of the endometrium, particularly in the tumors that exhibit microsatellite instability, whereas beta-catenin mutations do not seem to be associated with such a phenomenon.

Cytoskeletal Proteins↗

Loss of heterozygosity at the RB-1 locus and pRB immunostaining in epithelial ovarian tumors: a molecular, immunohistochemical, and clinicopathologic study.

Alterations in the retinoblastoma gene (RB-1) are common in human neoplasia. The frequency of loss of heterozygosity (LOH) at the RB-1 locus on chromosome 13q14 was studied in a series of 51 epithelial ovarian tumors (10 benign, 7 borderline, and 34 malignant). LOH was scored by the absence or reduction of the signal to < 50% of one of the alleles in tumor DNA compared with normal DNA. LOH results were correlated with retinoblastoma protein (pRB) immunostaining. LOH at the RB-1 locus was observed in 9 tumors (17.6%), specifically in 1 of 7 borderline tumors and 8 of 34 ovarian carcinomas (23.5%). Among the malignant tumors, LOH occurred more frequently in carcinomas with serous differentiation (7/23; 30%). A heterogeneous (10% to 70% cells) or diffuse (> 70% cells) pRB immunostaining was less frequent in benign (1/10; 10%) and borderline (2/7; 28%) tumors than in ovarian carcinomas (15/34; 44%), an observation that correlated with the higher proliferative index in carcinomas than in benign and borderline tumors. However, lack or only focal (< 10% cells) pRB immunostaining occurred in the vast majority of tumors with LOH at the RB-1 locus (7/9; 77%), a finding that may suggest a tumor suppressor role for RB-1 in these tumors. The results suggest that RB-1 may play a role in a subset of ovarian carcinomas, particularly those exhibiting serous differentiation.

Adenocarcinoma, Clear Cell↗

HMG-CoA reductase activity in human liver microsomes: comparative inhibition by statins.

The aim of this study was to compare a number of vastatins, HMG-CoA reductase inhibitors, in human liver microsomes. HMG-CoA reductase activity was four times lower than the activity in untreated rat liver microsomes. Vastatins could be classified in this in vitro assay in three classes both in human and rat microsomes: the first one including cerivastatin with an IC50 of 6 nM, the second one with atorvastatin and fluvastatin (IC50) between 40 and 100 nM) and the third one containing pravastatin, simvastatin and lovastatin (IC50 between 100 and 300 nM).

Animals↗

Opposite behaviors of reactive metabolites of tienilic acid and its isomer toward liver proteins: use of specific anti-tienilic acid-protein adduct antibodies and the possible relationship with different hepatotoxic effects of the two compounds.

Tienilic acid (TA) is responsible for an immune-mediated drug-induced hepatitis in humans, while its isomer (TAI) triggers a direct hepatitis in rats. In this study, we describe an immunological approach developed for studying the specificity of the covalent binding of these two compounds. For this purpose, two different coupling strategies were used to obtain TA-carrier protein conjugates. In the first strategy, the drug was linked through its carboxylic acid function to amine residues of carrier proteins (BSA-N-TA and casein-N-TA), while in the second strategy, the thiophene ring of TA was attached to proteins through a short 3-thiopropanoyl linker, the corresponding conjugates (BSA-S-5-TA and betaLG-S-5-TA) thus preferentially presenting the 2, 3-dichlorophenoxyacetic moiety of the drug for antibody recognition. The BSA-S-5-TA conjugate proved to be 30 times more immunogenic than BSA-N-TA. Anti-TA-protein adduct antibodies were obtained after immunization of rabbits with BSA-S-5-TA (1/35000 titer against betaLG-S-5-TA in ELISA). These antibodies strongly recognized the 2, 3-dichlorophenoxyacetic moiety of TA but poorly the part of the drug engaged in the covalent binding with the proteins. This powerful tool was used in immunoblots to compare TA or TAI adduct formation in human liver microsomes as well as on microsomes from yeast expressing human liver cytochrome P450 2C9. TA displayed a highly specific covalent binding focused on P450 2C9 which is the main cytochrome P450 responsible for its hepatic activation in humans. On the contrary, TAI showed a nonspecific alkylation pattern, targeting many proteins upon metabolic activation. Nevertheless, this nonspecific covalent binding could be completely shifted to a thiol trapping agent like GSH. The difference in alkylation patterns for these two compounds is discussed with regard to their distinct toxicities. A relationship between the specific covalent binding of P450 2C9 by TA and the appearance of the highly specific anti-LKM2 autoantibodies (known to specifically recognize P450 2C9) in patients affected with TA-induced hepatitis is strongly suggested.

Animals↗

Indiana pouch in female patients with spinal cord injury.

OBJECTIVE: We assessed the results of a continent urinary diversion (Indiana pouch) in seven women with severe neurogenic urinary incontinence. PATIENTS AND METHODS: There were seven patients (mean follow-up 28 months), in five of whom a complete Indiana pouch was created. In two the bladder was augmented with the Indiana pouch, the bladder neck was closed and an umbilical stoma was created. In three cases the appendix served as outlet whereas in the other patients a continent catheterisable stoma was created by means of a tapered terminal ileum. RESULTS: All the patients were dry (the stoma was continent) and could catheterise themselves while sitting in a wheelchair. There was one complication (bleeding) immediately postoperatively that needed reintervention. The late complications were acceptable: in one patient a stone had to be removed from the pouch and there was a stenosis of the stoma in two others. There was no hyperchloraemic acidosis. CONCLUSION: The Indiana pouch is a safe and effective method for neurogenic incontinence when all available pharmacological treatments and clean intermittent catheterisation have failed. It has little impact on the body image, and the independence and social reintegration of the woman is improved.

Adult↗

Intestinal volvulus in dogs: a study of four clinical cases.

Four cases of intestinal volvulus in German shepherd dogs are described. A definitive diagnosis was achieved by exploratory laparotomy in three cases and after necropsy in the remaining animal. Clinical signs, laboratory investigations and radiological changes are reported for three of the dogs. These dogs were all euthanased. Treatment of complete intestinal volvulus is difficult. By the time the condition is diagnosed, the pathological changes are irreversible, with consequent poor prognosis.

Animals↗

Sustentacular cells occur frequently in the familial form of medullary thyroid carcinoma.

The presence and distribution of S-100-immunoreactive sustentacular cells were investigated by immunohistochemistry in 67 medullary thyroid carcinomas (MTCs). The familial or sporadic status of the tumours was assessed by clinical data and confirmed by the identification of RET germline mutations using the polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and restriction analysis. Sustentacular cells were detected in 19 tumours (28.3 per cent). They were found significantly more frequently in the familial (15/24, 62.5 per cent) than in the sporadic MTCs (4/43, 9.3 per cent). The results indicate that sustentacular cells are commonly found in familial MTC and their presence in any MTC may be regarded as an indirect indicator that the tumour might be of the familial type.

Carcinoma, Medullary↗

Müllerian inhibiting substance, alpha-inhibin, and CD99 expression in sex cord-stromal tumors and endometrioid ovarian carcinomas resembling sex cord-stromal tumors.

Müllerian inhibiting substance (MIS), alpha-inhibin, and CD99 are expressed by normal and neoplastic sex cord and stromal gonadal derivatives. The expression of MIS, inhibin, and CD99 was evaluated by immunohistochemistry in a series of 19 sex cord-stromal tumors and seven ovarian endometrioid carcinomas resembling sex cord-stromal tumors. Normal ovaries and testes from patients with the androgen insensitivity syndrome were used as control. All three markers were detected in primordial ovarian follicles and immature seminiferous tubules. Both inhibin and MIS were expressed by all sex cord-stromal tumors, but inhibin immunostaining appeared stronger and more diffusely distributed. CD99 was expressed by all adult and juvenile granulosa cell tumors, but only focally by Sertoli-Leydig cell tumors. In Sertoli-Leydig cell tumors, the three markers were predominantly expressed by the Sertoli cells. None of the seven endometrioid carcinomas with a sex cord-stromal pattern was positive for MIS or inhibin; two of them reacted for CD99, but their staining patterns were not membranous. Inhibin immunoreactivity was also detected in foci of stromal luteinization, occasionally present in these tumors. MIS, inhibin, and CD99 are potentially useful markers in the differential diagnosis between sex cord-stromal tumors and endometrioid carcinomas resembling sex cord-stromal tumors.

12E7 Antigen↗

Development of new muscle synergies in postural control in spinal cord injured subjects.

The development of new patterns of postural control in patients with a complete thoracic spinal cord injury (SCI) during their active clinical rehabilitation was studied. Especially the role of non-postural muscles, like the latissimus dorsi (LD) and the trapezius pars ascendens (TPA), in maintaining and restoring sitting balance during standardized bimanual task performance was investigated. Twelve patients, diagnosed with an acute complete thoracic SCI between spinal cord level T2 and T12, participated in a longitudinal experimental study. Changes in the centre of pressure (CP) and electromyographic activity of the erector spinae (ES) at level L3, T9 and T3, the LD, the TPA, the pectoralis major (PM), the serratus anterior and the oblique abdominal muscles were investigated at several moments in the rehabilitation process. Results show a gradual development of specific muscle activation patterns for both high and low thoracic SCI patients. These patterns seem to be related to a combination of restoration of function of the ES-L3 and ES-T9 in the low thoracic SCI subjects and increased compensatory muscle use of the LD, TPA and PM in high SCI patients. The range in which low thoracic SCI patients can actively vary their CP increased slightly during rehabilitation.

Adolescent↗

[Microcirculatory consequences of a venous striction in the rat. Effect of a coumarine-rutine association].

The aim of this study was to investigate the consequences of a venous striction on capillary red blood cell distribution and venular blood return and the effect of a coumarin derivative-rutoside combination. The study was conducted, in vivo, in the rat cremaster muscle using intravital microscopy. The striction lasted thirty minutes and was obtained by clamping the epigastric vein. This mechanical constraint was sufficient to induce microcirculatory modifications without disrupting microvessels. Before the striction (t-5 min), the velocities and diameters of the veins and arteries were comparable in all groups. After the striction (t5 min), in the control group, venous blood flow decreased by 60%, from 0.48 +/- 0.09 mm3/s (t-5 min) to 0.20 +/- 0.06 mm3/s (t5 min). The results showed that after thirty minutes reperfusion, venular blood flow in the control animals was only 34% of initial blood flow. The mean red blood cell velocity dropped by 56%, the percentage of low perfused capillaries increased from 7.5% to 50%. Treatment of animals with a coumarin derivative-rutoside combination, particularly at 4 mg/kg coumarin derivative-100 mg/kg rutoside, has significantly improved the microcirculation. After thirty minutes reperfusion venular blood flow was 60% and the percentage of low perfused capillaries was only 10%. The effect seemed to be more pronounced for rutoside than coumarin derivatives. The interest of this study was to set up an experimental model of a venous striction not too severe to induce micro-hemorrages but enough to modify microcirculation. This model was used to quantify the beneficial effects of a coumarin derivative-rutoside combination.

Animals↗

Human anti-mitochondria autoantibodies appearing in iproniazid-induced immunoallergic hepatitis recognize human liver monoamine oxidase B.

Anti-mitochondria (anti-M6) autoantibodies have been found in the serum of patients with immunoallergic iproniazid (Marsilid)-induced hepatitis, but to date the identity of the protein antigen has not been determined. Here we show, using immunoprecipitation of pargyline-labelled proteins, that among the mitochondrial proteins, liver MAO-B is specifically recognized by the sera containing anti-M6 antibodies. Moreover the enzymatic activity of MAO-B towards phenylethylamine and tyramine is also suppressed after this immunoprecipitation, contrary to the MAO-A activity towards 5-hydroxy-tryptamine. As MAO is irreversibly inhibited by iproniazid, these results suggest that the mechanism of iproniazid-induced appearance of anti-M6 antibodies could be another example of the reactive metabolite/enzyme haptenization mechanism already proposed in the case of tienilic acid for the appearance of anti-organelle antibodies in a drug-induced hepatitis.

Antibody Specificity↗