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L Cartier

Publications and source records attributed to L Cartier.

At least 19 recordsLinked to original sources
PubMed2004

Presence of HTLV-I Tax protein in cerebrospinal fluid from HAM/TSP patients.

Infection with human T-cell lymphotropic virus type I (HTLV-I) have been associated with the development of the HTLV-I-associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP). The disease affects the pyramidal tract at the distal segments of spinal cord, generating a spastic paraparesis. We studied the presence of Tax protein in cerebrospinal fluid cells and spinal fluid (CSF) of 35 Chilean patients: 22 HAM/TSP patients (15 HTLV-I-seropositives, and 7 seronegatives), and 13 controls (9 PSP and 4 CJD non-infected patients). Tax antigens were evaluated with monoclonal antibodies reacting with Tax by immunofluorescence and ELISA assays in cerebrospinal fluid cells and CSF, respectively. Proviral was evaluated by PCR of tax gene in cerebrospinal fluid cells. Tax antigen was detected in CSF and lymphocytes of CSF from 4 and 12 HAM/TSP patients, respectively. Lymphocytes of CSF of 8 HAM/TSP (6 seropositives and 2 seronegatives) showed the presence of tax gene. These results show that cells of CSF from HAM/TSP patients are able to express and export Tax protein towards the CSF. This is the first report of the presence of Tax protein in cerebrospinal fluid cells and CSF from HAM/TSP HTLV-I seronegative patients.

Adult↗
PubMed2004

Neonatal diabetes, with hypoplastic pancreas, intestinal atresia and gall bladder hypoplasia: search for the aetiology of a new autosomal recessive syndrome.

AIMS/HYPOTHESIS: Neonatal diabetes is a rare disease with several identified molecular aetiologies. Despite associations with other malformations, neonatal diabetes with intestinal and biliary anomalies has not been described. The current study aims to describe a new syndrome, and to examine a possible link with one of three genes known to cause neonatal diabetes. METHODS: Five clinical cases are described. Immunohistochemical staining for pancreatic islet hormones was performed on three of the infants. DNA from one infant was analysed for abnormalities of the PLAGL-1 (ZAC), glucokinase and PDX-1 (IPF-1) genes. RESULTS: Five infants (two sibling pairs from two families, and an isolated case) presented with neonatal diabetes, hypoplastic or annular pancreas, jejunal atresia, duodenal atresia and gall bladder aplasia or hypoaplasia. One sibling pair was born to consanguineous parents. One patient with a milder form is surviving free of insulin. Four children died in the first year of life despite aggressive medical management. Pancreatic immunohistochemistry revealed few scattered chromogranin-A-positive cell clusters but complete absence of insulin, glucagon and somatostatin. Exocrine histology was variable. In one case from the consanguineous family, molecular analysis showed no duplication or uniparental isodisomy of PLAGL-1 at 6q24, no contiguous gene deletion involving the glucokinase gene, and no mutation in the coding sequences or splice sites of PDX-1. CONCLUSIONS/INTERPRETATION: This combination of multiple congenital abnormalities has not been previously described and probably represents a new autosomal recessive syndrome involving a genetic abnormality that interferes with normal islet development and whose aetiology is as yet unknown.

Abnormalities, Multiple↗
PubMed2004

In vitro cytoskeleton changes of mouse neurons induced by purified HTLV-1, and PBMC from HAM/TSP patients and HTLV-1 carriers.

HTLV-1 is the causative agent of HAM/TSP. This neurological disease affects the CNS producing damage of the motor tracts at the spinal cord. The HAM/TSP pathogenesis remains undefined. It could include direct and indirect actions of HTLV-1. We studied the effect of purified HTLV-1 and the PBMC of 22 Chilean patients co-cultivated with fetal neurons of mouse (CNh cells): 8 HAM/TSP, 8 HTLV-1 carriers, and 6 non-infected controls. The viral antigens and provirus in CNh cells was evaluated with monoclonal and polyclonal antibodies reacting with HTLV-1 by immunofluorescence assay and PCR at 0, 7 and 15 days of co-cultures, respectively. Viral antigens were detected in 0.1-0.5%, and 0-0.3% of the neurons incubated with lymphocytes of HAM/TSP patients and HTLV-1 carriers, respectively. Neurons incubated with cells of 7 HAM/TSP patients, and 3 HTLV-1 carriers showed the presence of nucleotide sequences of tax gene. These results would be showing that CNh cells would express viral antigens and provirus. The HTLV-1 or their proteins were capable in vitro to produce structural and growth changes in the cytoskeleton of CNh neurons. In this series, the purified HTLV-1 was more effective in the neural changes than PBMC of HAM/TSP or HTLV-1 carriers.

Animals↗
PubMed2004

Extracellular matrix protein expression in cerebrospinal fluid from patients with tropical spastic paraparesis associated with HTLV-I and Creutzfeldt-Jakob disease.

The cerebrospinal fluid (CSF) is in direct contact with the extracellular space of the CNS, thus biochemical processes in the CNS could potentially be reflected in the CSF. Changes in extracellular matrix (ECM) proteins can be studied through their analysis in the CSF. ECM plays an essential role in CNS homeostasis and several proteins such as laminin (LN), fibronectin (FN), thrombospondin (TS) and heparan sulphate proteoglycan (HS, perlecan) form part of its structure. Possible changes in the levels of these proteins were investigated in two different pathologies--tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM) (n=25) and Creutzfeldt-Jakob disease (CJD) (n=19)--and compared with those in a control group with or without neurological disease (n=25). CSF analyses were carried out using monoclonal or monospecific polyclonal antibodies. In comparison with the control group, it was found that TSP/HAM patients presented significantly higher levels of LN, TS and HS, while in CJD patients the levels of FN, TS and HS were increased. In CJD patients the HS level was almost double that of the TSP/HAM patients. These results suggest a distinct pattern of ECM proteins in CSF in relation to the type of neurological disease. TSP/HAM is a chronic motor disease that affects the white matter of the spinal cord, while CJD is a subacute dementia that affects cerebral neurons and their synapsis.

Adult↗
PubMed2003

Defective human T-cell lymphotropic virus type I (HTLV-I) provirus in seronegative tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM) patients.

Infection with human T-cell lymphotropic virus type I (HTLV-I) have been associated with the development of the tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM). We studied the presence of HTLV-I provirus in peripheral blood mononuclear cells (PBMC) from 72 Chilean patients with progressive spastic paraparesis by polymerase chain reaction: 32 seropositive and 40 seronegative cases. We amplified different genomic regions of HTLV-I using primers of 5' ltr, tax, env/tax, pX, pol and env genes. These genes were detected from all seropositive patients. The seronegative patients were negative with 5' ltr, pol, env, and pX primers. However, amplified product of tax and env/tax genes was detected from 16 and four seronegative patients, respectively. Three of them were positive with both genetic regions. The results of this study show that the complete HTLV-I provirus is found in 100% of seropositive cases. In seronegative cases, clinically very similar of seropositive cases, was found only tax gene in 42.5% (17/40) of patients. These results suggest the presence of a defective HTLV-I provirus in some seronegative patients with progressive spastic paraparesis, and suggest a pathogenic role of this truncate provirus for a group of TSP/HAM.

Adult↗
PubMed2002

Genetic characterization and phylogeny of human T-cell lymphotropic virus type I from Chile.

Infection with Human T-Cell Lymphotropic Virus type I (HTLV-I) have been associated with the development of the HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). Phylogenetic analyses of HTLV-I isolates have revealed that HTLV-I can be classified into three major groups: the Cosmopolitan, Central African and Melanesian. In the present study, we analyzed the tax, 5' ltr, gag, pol, and env sequences of proviruses of PBMC from ten HAM/TSP patients to investigate the phylogenetic characterization of HTLV-I in Chilean patients. HTLV-I provirus in PBMC from ten Chilean patients with HAM/TSP were amplified by PCR using primers of tax, 5' ltr, gag, pol, and env genes. Amplified products of the five genes were purified and nucleotide sequence was determined by the dideoxy termination procedure. DNA sequences were aligned with the CLUSTAL W program. The results of this study showed that the tax, 5' ltr, gag, pol, and env gene of the Chilean HTLV-I strains had a nucleotide homology ranged from 98.1 to 100%, 95 to 97%, 98.9 to 100%, 94 to 98%, and 94.2 to 98.5% respect to ATK-1 clone, respectively. According to molecular phylogeny with 5' ltr gene, the Chilean HTLV-I strains were grouped with each other suggesting one cluster included in Transcontinental subgroup.

Adult↗
PubMed2002

Comparative study of the epileptogenic effect of kainic acid injected into the cerebral cortex, hippocampus and amygdala in adult cats chronically implanted.

Intracerebral injection of kainic acid in cerebral cortex, hippocampus or amygdala in cats chronically implanted showed that: 1) Hippocampus and amygdala presented a greater sensitivity than the cerebral cortex, while hippocampus presented a greater sensitivity than the amygdala to the generation of an epileptic focus. 2) Comparison of latency, mean duration of afterdischarges, and the mean time period to obtain the peak intensity of the afterdischarge in the three cited structures, showed that mean latency of the first afterdischarge was significantly shorter in hippocampus and amygdala compared with the cerebral cortex. Moreover the mean time period to reach the peak intensity of the afterdischarge was again shorter in the subcortical structures. 3) The epileptic foci both in hippocampus and amygdala were blocked by CNQX and muscimol. 4) The behavioral changes depended on the intensity of the epileptic process. Tonic-clonic convulsions appeared only when the motor cerebral cortex was involved. Finally, 5) kainic acid injections in hippocampus and amygdala elicited an intense neuronal destruction and gliosis of these structures. We conclude that intracerebral injection of low doses of kainic acid in cats represent a good model to study focal epileptic thresholds in the CNS.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2002

Induction and blockade of epileptic foci by intracerebral injection of glutamatergic agonists and antagonists in frerly moving cats.

The aim of the present work was to test in adult cats the capability of three glutamatergic agonists, NMDA, AMPA and ACDP as epileptogenic agents. Drugs were microinjected in amygdala or hippocampus, and once generated an epileptic focus three selective glutamatergic antagonists NMDA, CNQX and MCPG, were tested. Before and after injection both the EEG and the behavior were continuously monitored. The results were as follows: 1) AMPA showed a greater capability than NMDA or ACPD to generate a chronic epileptic focus; 2) AMPA elicited a greater epileptogenic effect in hippocampus than in amygdala; NMDA had similar epileptogenic effect in both cited structures, and ACPD had not effect; 3) of the three glutamatergic antagonists used to block a long lasting focus, the most effective one was CNQX, which showed a greater effect in hippocampus than in amygdala; 4) comparison between the epileptogenic effect of AMPA and kainic acid (first paper) in the same structure, showed that kainic acid is about 15 fold more epileptogenic. A discussion of the probable mechanisms of these results was undertaken.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2001

[HTLV-I seronegative idiopathic progressive spastic paraparesis: clinical and neurophysiological study of the sensory features].

BACKGROUND: HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a defined entity. However, there are many patients not well characterized with a similar clinical picture who are HTLV-I seronegative. OBJECTIVE: Clinical and neurophysiological description of patients with HTLV-I seronegative idiopathic paraparesis. PATIENTS AND METHODS: Seventeen patients (4 women and 13 men aged 24-67 years, average 52.3) were evaluated including clinical assessment, vibratory sensory analysis, quantitative somatosensory thermotest (QST), somatosensory evoked potentials (SSEPs), electromyography (EMG) and motor and sensory nerve conductions. RESULTS: In addition to the spastic paraparesis, 3 (17.6%) patients had pseudobulbar symptoms. Ten (58.8%) patients had a spastic gait but could walk unaided, 6 (35.2%) needed support and 1 patient could not walk. Bladder dysfunction was found in 10 (58.8) patients and sensory symptoms in 7 (41.1%). There was mild distal impairment of vibration and position sense, distal tactile and pinprick hypoesthesia in 4 (23.4%) patients. Tibial SSEPs were abnormal in 11 (64.7%). Nerve conduction studies and EMG were normal. QST showed cold hypoesthesia in 14 (82.4%) patients. Warm sensation and beat pain appeared unimpaired. CONCLUSIONS: All sensory abnormalities found were restricted to sensations carried by myelinated (A beta and A delta) channels. Sensory and motor abnormalities are similar to HAM/TSP patients suggesting a common pathogenesis.

Adult↗
PubMed2001

Tropical spastic paraparesis.

Human T-cell lymphotropic virus type I (HTLV-I) is the cause of endemic tropical spastic paraparesis (TSP) or HTLV-I-associated myelopathy (HAM). Because TSP/HAM is not a fatal disease, the neuropathology of this disease, albeit relatively well understood, is based on the examination of just a few incidental cases. We summarise our experience with the neuropathology of tropical spastic paraparesis/HTLV-I associated myelopathy (TSP/HAM). We studied three cases of TSP/HAM from different parts of the world. We demonstrated peculiar lamellated structures, called "multilamellar bodies" (MLB). It is tempting to suggest that MLB may represent specific ultrastructural markers of TSP/HAM. The pathology of the anteriorand posterior horns was similar and comprised axonal degeneration, accompanied by extensive astrocytic gliosis. Lymphocytic infiltration, particularly observed as "cuffs" around blood vessels, was scattered among other cellular elements. Ultrastructurally, myelin sheaths were relatively well preserved, and some demyelinated but not remyelinated fibres were observed. Moreover, axons with abnormal accumulations of neurofilaments, suggestive of axonal degeneration, were detected. Several axons contained Hirano bodies. In many samples glial processes replaced most of the remaining neuropil.

Ganglia, Spinal↗
PubMed2000

Ancient HTLV type 1 provirus DNA of Andean mummy.

The worldwide geographic and ethnic clustering of patients with diseases related to human T cell lymphotropic virus type 1 (HTLV-1) may be explained by the natural history of HTLV-1 infection. The genetic characteristics of indigenous people in the Andes are similar to those of the Japanese, and HTLV-1 is generally detected in both groups. To clarify the common origin of HTLV-1 in Asia and the Andes, we analyzed HTLV-1 provirus DNA from Andean mummies about 1500 years old. Two of 104 mummy bone marrow specimens yielded a band of human beta-globin gene DNA 110 base pairs in length, and one of these two produced bands of HTLV-1-pX (open reading frame encoding p(40x), p(27x)) and HTLV-1-LTR (long terminal repeat) gene DNA 159 base pairs and 157 base pairs in length, respectively. The nucleotide sequences of ancient HTLV-1-pX and HTLV-1-LTR clones isolated from mummy bone marrow were similar to those in contemporary Andeans and Japanese, although there was microheterogeneity in the sequences of some mummy DNA clones. This result provides evidence that HTLV-1 was carried with ancient Mongoloids to the Andes before the Colonial era. Analysis of ancient HTLV-1 sequences could be a useful tool for studying the history of human retroviral infection as well as human prehistoric migration.

Asian People↗
PubMed2000

T lymphocytes activated by persistent viral infection differentially modify the expression of metalloproteinases and their endogenous inhibitors, TIMPs, in human astrocytes: relevance to HTLV-I-induced neurological disease.

Activation of T lymphocytes by human pathogens is a key step in the development of immune-mediated neurologic diseases. Because of their ability to invade the CNS and their increased secretion of proinflammatory cytokines, activated CD4+ T cells are thought to play a crucial role in pathogenesis. In the present study, we examined the expression of inflammatory mediators the cytokine-induced metalloproteinases (MMP-2, -3, and -9) and their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMP-1, -2, and -3), in human astrocytes in response to activated T cells. We used a model system of CD4+ T lymphocytes activated by persistent viral infection (human T lymphotropic virus, HTLV-I) in transient contact with human astrocytes. Interaction with T cells resulted in increased production of MMP-3 and active MMP-9 in astrocytes despite increased expression of endogenous inhibitors, TIMP-1 and TIMP-3. These data suggest perturbation of the MMP/TIMP balance. These changes in MMP and TIMP expression were mediated, in part, by soluble factors (presumably cytokines) secreted by activated T cells. Integrin-mediated cell adhesion is also involved in the change in MMP level, since blockade of integrin subunits (alpha1, alpha3, alpha5, and beta1) on T cells resulted in less astrocytic MMP-9-induced expression. Interestingly, in CNS tissues from neurological HTLV-I-infected patients, MMP-9 was detected in neural cells within the perivascular space, which is infiltrated by mononuclear cells. Altogether, these data emphasize the importance of the MMP-TIMP axis in the complex interaction between the CNS and invading immune cells in the context of virally mediated T cell activation.

Adult↗
PubMed2000

[Increased activity of metalloproteinases and their inhibitors in cerebrospinal fluid of patients with tropical spastic paraparesis].

BACKGROUND: Proteolytic modifications of neuronal surfaces and the surrounding extracellular matrix are very important in neuronal development and regeneration. Increased activity of matrix metalloproteinases (MMPs) and their tissue inhibitors, due to secretion by macrophages and lymphocytes, occur in inflammatory processes that disrupt the blood brain barrier. However, neurons and microglia can also secrete these enzymes. AIM: To identify the type of MMP present in the cerebrospinal fluid (CSF) and changes in the expression of tissue inhibitors of metalloproteinases (TIMPs) in patients with HTLV-1 associated tropical spastic paraparesis. PATIENTS AND METHODS: CSF samples from 12 patients with HTLV-1 associated tropical spastic paraparesis and 12 healthy controls were obtained by an atraumatic lumbar puncture. The presence of MMPs was measured by zymography and the relative amounts of TIMPs were measured by immunowestern blot. RESULTS: In the CSF of both controls and patients, a similar gelatinolytic band corresponding to proMMP-2 (latent form) was observed. In 83.3% of patients with HTLV 1 associated tropical spastic paraparesis, the MMP-9 was also present. TIMP-1, TIMP-2 and TIMP-3 were elevated 2.24 +/- 0.72, 3.85 +/- 1.38 and 5.89 +/- 3.4 fold, respectively, in the CSF of patients as compared to controls. CONCLUSIONS: Patients with HTLV-1 associated tropical spastic paraparesis have elevated activity of MMP-9 and levels of TIMPs in the CSF, when compared to healthy controls.

Adult↗
PubMed1999

The HIV Nef protein alters Ca(2+) signaling in myelomonocytic cells through SH3-mediated protein-protein interactions.

Human immunodeficiency virus Nef plays an important role in AIDS pathogenesis. In addition to the well known down-regulation of cell surface receptors (CD4, MHCI), Nef is able to alter cellular signaling. Of particular interest for this study is the ability of Nef to bind with a very high affinity to SH3 domains of myelomonocyte-specific protein-tyrosine kinases of the Src family (Src-like PTK). We have therefore investigated Ca(2+) signaling in HL60 cells retrovirally transduced with wild type Nef or with a Nef mutant deficient in the SH3-interacting proline-rich motif (Nef((PXXP)4(-))). In differentiated HL60 cells, Nef markedly altered cellular Ca(2+) signaling; the amount of intracellularly stored Ca(2+) was increased, and as a consequence, store-operated Ca(2+)-influx was decreased. This effect was not observed in undifferentiated HL60 cells or in CEM T-lymphocytes and correlated with the differentiation-induced up-regulation of Src-like PTK. The Nef effect on Ca(2+) signaling depended entirely on the integrity of its PXXP motif. The Src-like PTK p56/59(hck) co-immunoprecipitated with both Nef and with the inositol 1,4,5-trisphosphate receptor, providing a possible mechanistic link between the viral protein and intracellular Ca(2+) stores of the host cell. Collectively, our results demonstrate that the human immunodeficiency virus 1 Nef protein manipulates intracellular Ca(2+) stores through SH3-mediated interactions in myelomonocytic cells.

Calcitriol↗
PubMed1999

Characteristic distribution of HTLV type I and HTLV type II carriers among native ethnic groups in South America.

To confirm the geographic and ethnic segregation of HTLV-I and HTLV-II carriers in native populations in South America, we have conducted a seroepidemiological study of native populations in South America, including HTLV-I carriers distributed among seven ethnic groups in the Andes highlands of Colombia, Peru, Bolivia, Argentina, and Chile, and two ethnic groups on Chiloe Island and Easter Island; and HTLV-II carriers distributed among seven ethnic groups of the lowlands along the Atlantic coast of Colombia, Orinoco, Amazon, and Patagonia, and one ethnic group on Chiloe Island. The incidence rate of HTLV-I and HTLV-II carriers varied among the ethnic groups, ranging from 0.8 to 6.8% for HTLV-I seropositivity and from 1.4 to 57.9% for HTLV-II seropositivity. A new HTLV-I focus was found among the Peruvian Aymara (1.6%), the Bolivian Aymara (5.3%) and Quechua (4.5%), the Argentine Puna (2.3%), and the Chilean Atacama (4.1%), while on HTLV-II focus was found among the Brazilian Kayapo (57.9%), the Paraguayan Chaco (16.4%), and the Chilean Alacalf (34.8%) and Yahgan (9.1%). The distribution of HTLV-I/II foci showed a geographic clustering of HTLV-I foci in the Andes highlands and of HTLV-II foci in the lowlands of South America. It was thus suggested that South American natives might be divided into two major ethnic groups by HTLV-I and HTLV-II carrier state.

Adolescent↗
PubMed1999

Dynamical scattering and electron diffraction from thin polymer lamellar crystals - poly(tert-butylethylene sulfide).

Strong violations of Friedel symmetry are observed in hk0 electron diffraction patterns from lamellar crystals of poly(tert-butylethylene sulfide) obtained at 120 kV. These deviations are largely explained by a multislice dynamical scattering calculation based on the crystal structure model. Further improvement is found when a secondary scattering component is added, in keeping with a perfect crystallite thickness less than that of the lamellar thickness. Despite the multiple-scattering perturbations, the frustrated chain packing can still be determined by direct methods followed by Fourier refinement. However, the Friedel-related intensities must be averaged before calculation of normalized structure factors.

Journal Article↗
PubMed1999

The presence of ancient human T-cell lymphotropic virus type I provirus DNA in an Andean mummy.

The worldwide geographic and ethnic clustering of patients with diseases related to human T-cell lymphotropic virus type I (HTLV-I) may be explained by the natural history of HTLV-I infection. The genetic characteristics of indigenous people in the Andes are similar to those of the Japanese, and HTLV-I is generally detected in both groups. To clarify the common origin of HTLV-I in Asia and the Andes, we analyzed HTLV-I provirus DNA from Andean mummies about 1,500 years old. Two of 104 mummy bone marrow specimens yielded a band of human beta-globin gene DNA 110 base pairs in length, and one of these two produced bands of HTLV-I-pX (open reading frame encoding p40x, p27x) and HTLV-I-LTR (long terminal repeat) gene DNA 159 base pairs and 157 base pairs in length, respectively. The nucleotide sequences of ancient HTLV-I-pX and HTLV-I-LTR clones isolated from mummy bone marrow were similar to those in contemporary Andeans and Japanese, although there was microheterogeneity in the sequences of some mummy DNA clones. This result provides evidence that HTLV-I was carried with ancient Mongoloids to the Andes before the Colonial era. Analysis of ancient HTLV-I sequences could be a useful tool for studying the history of human retroviral infection as well as human prehistoric migration.

Asian People↗