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S Martinez

Publications and source records attributed to S Martinez.

At least 19 recordsLinked to original sources
PubMed2006

Sonic hedgehog from the basal plate and the zona limitans intrathalamica exhibits differential activity on diencephalic molecular regionalization and nuclear structure.

The diencephalon is the most complex area of the vertebrate brain, being particularly complex in amniotes. It has been suggested that diencephalic regionalization partially depends on local signaling mediated by sonic hedgehog (Shh). However, since the Shh gene is expressed in both the diencephalic basal plate and the zona limitans intrathalamica (ZLI), it is still unclear which of these tissues exerts morphogenetic influence on thalamic regionalization. In the present study using chick and quail embryos, we have found that although Shh from the ZLI and the basal plate induces ectopic expression of diencephalic genes in the posterior prosencephalic alar plate, only Shh originating from the ZLI can induce ectopic gene expression in the anterior alar plate, indicating that the ZLI exerts specific activity in the anterior epithelium. By introducing microbarriers between the diencephalic alar neuroepithelium and either the ZLI or the basal plate, we generated local loss of Shh expression in the ZLI, leading to alterations in molecular regionalization and subsequently, in the nuclear organization of the alar diencephalic derivatives on both sides of the ZLI. We thus demonstrate in vivo that basal signals are required to induce Shh expression in the ZLI and that Shh from the ZLI plays a pivotal role in regionalizing the alar diencephalon. The structural phenotype of Shh abolition in the ZLI consisted of a progressive pattern of alterations in diencephalic organization which were associated with the observed gradient effects in the molecular regionalization of the diencephalon. We conclude that the ZLI is a secondary organizer which exerts its morphogenetic activity through Shh.

Animals↗
PubMed2006

Gene duplications in 21-hydroxylase deficiency: the importance of accurate molecular diagnosis in carrier detection and prenatal diagnosis.

BACKGROUND: The detection of 21-OH deficiency (21OHD) carriers in the general population requires that misinterpretations of apparently severe mutations in alleles carrying duplicated genes be avoided. Prenatal treatment prevents virilization in female fetuses and genetic counseling may be offered to couples in which one partner is either a patient or a carrier. This paper proposes a semiquantitative PCR method involving primer extension that distinguishes the severe point mutation Q318X in single gene copy alleles from the normal/nondeficient variant in gene-duplicated alleles. SAMPLES AND METHODS: DNA from 65 individuals carrying Q318X variants, that of 85 partners of 21OHD carriers or patients, and one fetal sample (as well as the DNA of his family) were analyzed. 21OHD alleles were studied by gene-specific PCR/allele-specific oligonucleotides hybridization for common mutations, Southern analysis, complementary direct sequencing and microsatellite typing. Primer extension analysis of the Q318X variants using fluorescent dideoxynucleotides was performed on CYP21A2 gene-specific PCR-amplified DNA samples from controls, patients, potential carriers and prenatal samples. RESULTS: Different fluorescence patterns were seen for the severe mutation (single gene copy) and the nondeficient (gene-duplicated) alleles carrying Q318X. The normal/mutant fluorescence peak (N/M) ratio was < 1 in all heterozygous carriers (mean 0.83; min. 0.70; max. 0.95). In all normal individuals carrying the gene-duplicated Q318X normal variant, the N/M ratio was > 1 (mean 1.69; min. 1.44; max. 2.02). CONCLUSION: The proposed method discriminated between the severe Q318X mutation and the normal Q318X variant in gene duplication, and could be a useful complementary tool in prenatal diagnosis and carrier detection.

Adrenal Hyperplasia, Congenital↗
PubMed2004

Magnetic resonance imaging of intramuscular myxoma with histological comparison and a review of the literature.

OBJECTIVE: To evaluate the magnetic resonance (MR) features of intramuscular myxoma (IM) compared with its pathological findings. DESIGN: Two radiologists retrospectively reviewed records and imaging studies of patients with histologically proven IM. Two radiologists also analyzed by consensus all the MR studies (pre- and post-contrast T1-weighted and T2-weighted sequences) and a pathologist reviewed the available histological material. PATIENTS: Seventeen patients with 18 histologically proven IM were reviewed. Histological samples of 11 of these 18 tumors were available for pathological analysis. RESULTS: There were 14 women and three men, with a mean age of 58.9 years. IM involved predominantly the thigh (n=10). MR imaging showed well-circumscribed intramuscular masses, hypointense on T1-weighted and hyperintense on T2-weighted images. Eleven masses were homogeneous and seven slightly heterogeneous due to fibrous septa. Enhanced MR imaging demonstrated three different patterns: peripheral enhancement (n=1), peripheral and patchy internal enhancement (n=7) or peripheral and linear internal enhancement (n=4). Intratumoral cysts were detected in four masses. MR imaging showed the presence of a pseudocapsule (n=12), fat around the lesion (n=16) and peritumoral edema (n=16). Histologically, all the tumors were hypocellular, hypovascular and myxoid. Peripheral areas of collagenous fibers formed a partial capsule and IM often merged into surrounding muscular fibers. More cellular tumors and those with scanty myxoid stroma tended to show a more prominent internal enhancement. CONCLUSION: IM shows several recognizable MR features which suggest its diagnosis.

Adipose Tissue↗
PubMed2004

Ezrin gene, coding for a membrane-cytoskeleton linker protein, is regionally expressed in the developing mouse neuroepithelium.

Ezrin is a member of the Ezrin, Radixin, Moesin (ERM) proteins family that are proposed to act as linkers between the cytoskeleton and plasma membrane. Ezrin regulates cell-cell and cell-matrix interactions playing a role in the regulation of cellular adhesion, movement and morphology in epithelia. Alterations in the expression of Ezrin and other members of ERM family have also been observed in brain tumours. Here we report the expression pattern of Ezrin during mouse neural development, from early stages to postnatal stages. In young and middle gestation embryos, Ezrin is expressed in the roof plate of the neural tube, in the presumptive domain of the choroidal plexus, and in some precise domains of ventricular epithelium. These domains are distributed in basal and alar neuroepithelial regions, some of them in relation to the expression of cadherins. At later gestation and postnatal stages, Ezrin expression is maintained on the mature choroidal plexus and is weakly detected in the proliferative regions of the mature brain.

Animals↗
PubMed2003

The evolution of dispersal.

A non-local model for dispersal with continuous time and space is carefully justified and discussed. The necessary mathematical background is developed and we point out some interesting and challenging problems. While the basic model is not new, a 'spread' parameter (effectively the width of the dispersal kernel) has been introduced along with a conventional rate paramter, and we compare their competitive advantages and disadvantages in a spatially heterogeneous environment. We show that, as in the case of reaction-diffusion models, for fixed spread slower rates of diffusion are always optimal. However, fixing the dispersal rate and varying the spread while assuming a constant cost of dispersal leads to more complicated results. For example, in a fairly general setting given two phenotypes with different, but small spread, the smaller spread is selected while in the case of large spread the larger spread is selected.

Animals↗
PubMed2002

Is obesity a high-risk factor for laparoscopic colorectal surgery?

BACKGROUND: The aim of this study was to assess the outcome of laparoscopic colorectal surgery in obese patients and compare it to that of a nonobese group of patients who underwent similar procedures. METHODS: All 162 consecutive patients who underwent an elective laparoscopic or laparoscopic-assisted segmental colorectal resection between August 1991 and December 1997 were evaluated. Body mass index (BMI; kg/m2) was used as an objective index to indicate massive obesity. The parameters analyzed included BMI, age, gender, comorbid conditions, diagnosis, procedure, American Society of Anesthesiologists classification score, operative time, estimated blood loss, transfusion requirements, intraoperative complications, conversion to laparotomy, postoperative complications, length of hospitalization, and mortality. RESULTS: Thirty-one patients (19.1%) were obese (23 males and 8 females). Conversion rates were significantly increased in the obese group (39 vs 13.5%, p = 0.01), with an overall conversion rate of 18%. The postoperative complication rate in the obese group was 78% versus 24% in the nonobese group (p <0.01). Specifically, rates of ileus and wound infections were significantly higher in the obese group [32.3 vs. 7.6% (p <0.01) and 12.9 vs 3.1%. (p = 0.03), respectively]. Furthermore, hospital stay in the obese group was longer (9.5 days) than in the nonobese group (6.9 days, p = 0.02). CONCLUSION: Laparoscopic colorectal segmental resections are feasible in obese patients. However, increased rates of conversion to laparotomy should be anticipated and the risk of postoperative complications is significantly increased, prolonging the length of hospitalization when compared to that of nonobese patients.

Adolescent↗
PubMed2002

LIS1-no more no less.

LIS1 is one of the genes that has a principle role in brain development since hemizygote mutations in LIS1 result in a severe brain malformation known as lissencephaly ('smooth brain'). LIS1 is a WD repeat protein and is known to be involved in several protein complexes that are likely to play a functional role in brain development. We discuss here the brain developmental phenotype observed in mice heterozygote for an N-terminal truncated LIS1 protein in view of known LIS1 protein interactions.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2001

Targeted mutagenesis of Lis1 disrupts cortical development and LIS1 homodimerization.

Lissencephaly is a severe brain malformation in humans. To study the function of the gene mutated in lissencephaly (LIS1), we deleted the first coding exon from the mouse Lis1 gene. The deletion resulted in a shorter protein (sLIS1) that initiates from the second methionine, a unique situation because most LIS1 mutations result in a null allele. This mutation mimics a mutation described in one lissencephaly patient with a milder phenotype. Homozygotes are early lethal, although heterozygotes are viable and fertile. Most strikingly, the morphology of cortical neurons and radial glia is aberrant in the developing cortex, and the neurons migrate more slowly. This is the first demonstration, to our knowledge, of a cellular abnormality in the migrating neurons after Lis1 mutation. Moreover, cortical plate splitting and thalomocortical innervation are also abnormal. Biochemically, the mutant protein is not capable of dimerization, and enzymatic activity is elevated in the embryos, thus a demonstration of the in vivo role of LIS1 as a subunit of PAF-AH. This mutation allows us to determine a hierarchy of functions that are sensitive to LIS1 dosage, thus promoting our understanding of the role of LIS1 in the developing cortex.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2001

Fine-needle aspiration cytology of pseudosarcomatous lesions of soft tissue.

Pseudosarcomatous lesions are benign neoplasms of the musculoskeletal system that are likely to be misdiagnosed as malignant, based on clinical and histologic features. These include soft-tissue "tumors" considered reactive or reparative lesions such as nodular fasciitis and myositis ossificans. Also included in the "pseudosarcoma" category are benign neoplasms which show "pseudoanaplastic" cytologic atypia. The latter include lipoma, leiomyoma, angiomyolipoma, and benign peripheral nerve-sheath tumors. These neoplasms, particularly the reparative processes and the nerve sheath tumors, are increasingly being subjected to initial diagnosis by fine-needle aspiration cytology. Even by conventional cytology this group of lesions represents a well-known pitfall for the diagnostic pathologist. We review some cytologic features: repair-like change, cohesion of cellular fragments, and presence of "normal" elements in the aspirate, which may help the cytopathologist avoid misdiagnosis of these notoriously difficult entities.

Biopsy, Needle↗
PubMed2001

Ability of peripheral DXA measurements of the forearm to predict low axial bone mineral density at menopause.

The aim of this study was to evaluate the ability of peripheral dual-energy X-ray absorptiometry (pDXA) measurement of the forearm to predict low axial bone mineral density (BMD) as defined according to the WHO classification. Two hundred and thirty-four healthy women aged 45-60 years were investigated. BMD was measured at the proximal and distal radius + ulna by pDXA and at the lumbar spine and femoral neck by DXA. There was a significant but moderate correlation between peripheral and axial BMD measurements, with r values ranging from 0.4 to 0.6 (SEE: 13.5-17%). The cutoff values for the proximal and distal radius BMD that allow the identification with 95% sensitivity of postmenopausal women with either a lumbar spine or femoral neck T-score < -1, corresponded to a T-score of +0.5 (proximal radius) and +1 (distal radius). More than 90% of the whole population had a peripheral T-score below these thresholds. Using an axial T-score < or = -2.5 as the definition of abnormality reduced to 48% (proximal radius) to 66% (distal radius) the number of women who would have required DXA axial measurements (i.e., with a pDXA T-score below the cutoff value of -0.7). Of the 33 women (14%) with a proximal radius T-score < or = -2.5 (osteoporosis), only 1 had a lumbar spine and femoral neck T-score > or = -1 (normal). Conversely, of the 50% (proximal radius) to 65% (distal radius) of the women with normal forearm measurement, 5% (proximal radius) to 9% (distal radius) were found to be osteoporotic and an additional 57% (proximal radius) to 59% (distal radius) could be classified as osteopenic (T-score between -1 and -2.5) at either the lumbar spine or femoral neck. In conclusion, use of pDXA forearm measurement as a prescreening tool in early postmenopausal women should allow the direct identification of about 50% of the women with no axial osteoporosis. However, this study highlights the difficulties in using a unique T-score that could be applied to different sites to diagnose osteoporosis.

Absorptiometry, Photon↗
PubMed2001

Vesicle-mediated trafficking of parasite proteins to the host cell cytosol and erythrocyte surface membrane in Plasmodium falciparum infected erythrocytes.

During the development of the asexual stage of the malaria parasite, Plasmodium falciparum, the composition, structure and function of the host cell membrane is dramatically altered, including the ability to adhere to vascular endothelium. Crucial to these changes is the transport of parasite proteins, which become associated with or inserted into the erythrocyte membrane. Protein and membrane targeting beyond the parasite plasma membrane must require unique pathways, given the parasites intracellular location within a parasitophorous vacuolar membrane and the lack of organelles and biosynthetic machinery in the host cell necessary to support a secretory system. It is not clear how these proteins cross the parasitophorous vacuolar membrane or how they traverse the erythrocyte cytosol to reach their final destinations. The identification of: (1) a P. falciparum homologue of the protein Sar1p, which is an essential component of the COPII-based secretory system in mammalian cells and yeast and (2) electron-dense, possibly coated, secretory vesicles bearing P. falciparum erythrocyte membrane protein 1 and P. falciparum erythrocyte membrane protein 3 in the host cell cytosol of P. falciparum infected erythrocytes recently provided the first direct evidence of a vesicle-mediated pathway for the trafficking of some parasite proteins to the erythrocyte membrane. The major advance in uncovering the parasite-induced secretory pathway was made by incubating infected erythrocytes with aluminium tetrafluoride, an activator of guanidine triphosphate-binding proteins, which resulted in the accumulation of the vesicles into multiple vesicle strings. These vesicle complexes were often associated with and closely abutted the erythrocyte membrane, but were apparently prevented from fusing by the aluminium fluoride treatment, making their capture by electron microscopy possible. It appears that malaria parasites export proteins into the host cell cytosol to support a vesicle-mediated protein trafficking pathway.

Animals↗
PubMed2001

Coordinate expression of Fgf8, Otx2, Bmp4, and Shh in the rostral prosencephalon during development of the telencephalic and optic vesicles.

Previous studies suggest that Fgf8 has a key role in regulating vertebrate development. In the rostral head of the embryonic chicken, there are increasing numbers of separate Fgf8 domains; these are present in tissues that appear to have previously expressed Otx2. As Fgf8 expression becomes established, Otx2 expression weakens, but remains in cells abutting the Fgf8 expression domain. These Fgf8 expression domains are closely associated with tissues expressing Bmp4 and Shh. Based on analogy with the embryonic limb, we suggest that Fgf8, Bmp4 and Shh function together in patterning regions of the embryonic head. Gene expression changes are particularly prominent in 14-21 somite stage embryos in the rostral forebrain, during early morphogenesis of the telencephalic and optic vesicles, when several new interfaces of Fgf8, Bmp4 and Shh are generated. To gain insights into the functions of fibroblast growth factor 8 (FGF8) in the embryonic forebrain, we studied the effects of implanting beads containing this protein in the dorsal prosencephalon of embryonic day 2 chicken embryos. Ectopic FGF8 had profound effects on morphogenesis of the telencephalic and optic vesicles. It disrupted formation of the optic stalk and caused a transformation of the pigment epithelium into neural retina. Within the telencephalon, FGF8 beads frequently induced a sulcus that had features of an ectopic rostral midline. The sulcus separated the telencephalon into rostral and caudal vesicles. Furthermore, we present evidence that FGF8 can regulate regionalization of the prosencephalon through inhibition of Otx2 and Emx2 expression. Thus, these experiments provide evidence that FGF8 can regulate both morphogenesis and patterning of the rostral prosencephalon (telencephalic and optic vesicles). FGF8 beads can induce midline properties (e.g. a sulcus) and can modulate the specification and differentiation of adjacent tissues. We suggest that some of these effects are through regulating the expression of homeobox genes (Otx2 and Emx2) that are known to participate in forebrain patterning.

Age Factors↗
PubMed2001

Antioxidant properties of alpha-crystallin.

alpha-Crystallin is a major chaperone lens protein to which has been ascribed antioxidant functions. In the present work we have evaluated the antioxidant and free radical scavenging properties of bovine alpha-crystallin in a series of in vitro models: zimosan-induced, luminol-enhanced chemiluminescence response of polymorphonuclear leukocytes, the autoxidation of brain homogenate, bleaching of 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)-derived radical cations, trapping of peroxyl radicals, and reactivity toward hypochloric acid. In all these systems, the reactivity of alpha-crystallin is higher than or similar to that of bovine serum albumin. It is concluded that, given the high concentrations of ol-crystallin in the lenses, its capacity to interact with free radicals and to remove hypochlorous acid could contribute to the maintenance of the lens functionality.

Animals↗
PubMed2001

The effect of thiamine supplementation on tumour proliferation. A metabolic control analysis study.

Thiamine deficiency frequently occurs in patients with advanced cancer and therefore thiamine supplementation is used as nutritional support. Thiamine (vitamin B1) is metabolized to thiamine pyrophosphate, the cofactor of transketolase, which is involved in ribose synthesis, necessary for cell replication. Thus, it is important to determine whether the benefits of thiamine supplementation outweigh the risks of tumor proliferation. Using oxythiamine (an irreversible inhibitor of transketolase) and metabolic control analysis (MCA) methods, we measured an in vivo tumour growth control coefficient of 0.9 for the thiamine-transketolase complex in mice with Ehrlich's ascites tumour. Thus, transketolase enzyme and thiamine clearly determine cell proliferation in the Ehrlich's ascites tumour model. This high control coefficient allows us to predict that in advanced tumours, which are commonly thiamine deficient, supplementation of thiamine could significantly increase tumour growth through transketolase activation. The effect of thiamine supplementation on tumour proliferation was demonstrated by in vivo experiments in mice with the ascites tumour. Thiamine supplementation in doses between 12.5 and 250 times the recommended dietary allowance (RDA) for mice were administered starting on day four of tumour inoculation. We observed a high stimulatory effect on tumour growth of 164% compared to controls at a thiamine dose of 25 times the RDA. This growth stimulatory effect was predicted on the basis of correction of the pre-existing level of thiamine deficiency (42%), as assayed by the cofactor/enzyme ratio. Interestingly, at very high overdoses of thiamine, approximately 2500 times the RDA, thiamine supplementation had the opposite effect and caused 10% inhibition of tumour growth. This effect was heightened, resulting in a 36% decrease, when thiamine supplementation was administered from the 7th day prior to tumour inoculation. Our results show that thiamine supplementation sufficient to correct existing thiamine deficiency stimulates tumour proliferation as predicted by MCA. The tumour inhibitory effect at high doses of thiamine is unexplained and merits further study.

Animals↗
PubMed2001

Monofocal origin of telencephalic oligodendrocytes in the anterior entopeduncular area of the chick embryo.

Oligodendrocytes are the myelin-forming cells in the central nervous system. In the brain, oligodendrocyte precursors arise in multiple restricted foci, distributed along the caudorostral axis of the ventricular neuroepithelium. In chick embryonic hind-, mid- and caudal forebrain, oligodendrocytes have a basoventral origin, while in the rostral fore-brain oligodendrocytes emerge from alar territories (Perez Villegas, E. M., Olivier, C., Spassky, N., Poncet, C., Cochard, P., Zalc, B., Thomas, J. L. and Martinez, S. (1999) Dev. Biol. 216, 98-113). To investigate the respective territories colonized by oligodendrocyte progenitor cells that originate from either the basoventral or alar foci, we have created a series of quail-chick chimeras. Homotopic chimeras demonstrate clearly that, during embryonic development, oligodendrocyte progenitors that emerge from the alar anterior entopeduncular area migrate tangentially to invade the entire telencephalon, whereas those from the basal rhombomeric foci show a restricted rostrocaudal distribution and colonize only their rhombomere of origin. Heterotopic chimeras indicate that differences in the migratory properties of oligodendroglial cells do not depend on their basoventral or alar ventricular origin. Irrespective of their origin (basal or alar), oligodendrocytes migrate only short distances in the hindbrain and long distances in the prosencephalon. Furthermore, we provide evidence that, in the developing chick brain, all telencephalic oligodendrocytes originate from the anterior entopeduncular area and that the prominent role of anterior entopeduncular area in telencephalic oligodendrogenesis is conserved between birds and mammals.

Animals↗
PubMed2000

Autoinhibition of a calmodulin-dependent calcium pump involves a structure in the stalk that connects the transmembrane domain to the ATPase catalytic domain.

The regulation of Ca(2+)-pumps is important for controlling [Ca(2+)] in the cytosol and organelles of all eukaryotes. Here, we report a genetic strategy to identify residues that function in autoinhibition of a novel calmodulin-activated Ca(2+)-pump with an N-terminal regulatory domain (isoform ACA2 from Arabidopsis). Mutant pumps with constitutive activity were identified by complementation of a yeast (K616) deficient in two Ca(2+)-pumps. Fifteen mutations were found that disrupted a segment of the N-terminal autoinhibitor located between Lys(23) and Arg(54). Three mutations (E167K, D219N, and E341K) were found associated with the stalk that connects the ATPase catalytic domain (head) and with the transmembrane domain. Enzyme assays indicated that the stalk mutations resulted in calmodulin-independent activity, with V(max), K(mATP), and K(mCa(2+)) similar to that of a pump in which the N-terminal autoinhibitor had been deleted. A highly conservative substitution at Asp(219) (D219E) still produced a deregulated pump, indicating that the autoinhibitory structure in the stalk is highly sensitive to perturbation. In plasma membrane H(+)-ATPases from yeast and plants, similarly positioned mutations resulted in hyperactive pumps. Together, these results suggest that a structural feature of the stalk is of general importance in regulating diverse P-type ATPases.

ATP-Binding Cassette Transporters↗
PubMed2000

Barhl1, a gene belonging to a new subfamily of mammalian homeobox genes, is expressed in migrating neurons of the CNS.

The BarH1 and BarH2 ( Bar ) Drosophila genes are homeobox-containing genes, which are required for the fate determination of external sensory organs in the fly. By means of a bioinformatic approach, we have identified in mouse and human two homeobox genes highly related to the Bar Drosophila genes, Barhl1 and Barhl2. While Barhl1 represents a novel gene, Barhl2 turned out to correspond to the mBH1 cDNA recently described in rat. We isolated and sequenced the full-length mouse Barhl1 and mapped both the human BARHL1 and BARHL2 genes to chromosomes 9q34 and 1p22, respectively. Detailed analysis of the murine Barhl1 expression pattern by in situ hybridization revealed that this transcript is exclusively expressed in restricted domains of the developing CNS, which suggests that this gene, similar to its Drosophila counterparts BarH1 and BarH2, may play a crucial role in cell fate determination of neural structures. In particular, Barhl1 showed specific domains of expression in the diencephalon and in the rhombencephalon where it was found to be expressed in migrating cells giving rise to the cerebellar external granular layer and to specific populations of dorsal sensory interneurons of the spinal cord. Thus, Barhl1 function may be required for the generation of these specific subtypes of neuronal progenitors. Furthermore, the mapping assignment and the expression pattern make BARHL1 an attractive positional candidate gene for a form of Joubert syndrome, a rare developmental anomaly of the cerebellum in humans.

Amino Acid Sequence↗