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Biomedical subjects

I Mendez

Publications and source records attributed to I Mendez.

34 records · Page 2Linked to original sources
PubMed1998

Enhancement of graft survival and sensorimotor behavioral recovery in rats undergoing transplantation with dopaminergic cells exposed to glial cell line-derived neurotrophic factor.

OBJECT: The goal of this study was to investigate the ability of fetal dopaminergic neurons to improve complex sensorimotor behavior. METHODS: The authors obtained ventral mesencephalic tissue from 14-day-old rat fetuses. The cells were exposed to glial cell line-derived neurotrophic factor (GDNF) prior to transplantation into rats with unilateral 6-hydroxydopamine lesions of the dopaminergic nigrostriatal pathway. Animals that received 400,000 cells exposed to GDNF demonstrated significant improvement in contralateral forelimb function and showed improvement in rotational behavior faster than animals that received cells not exposed to GDNF. Increasing the number of implanted cells to 800,000 exposed to GDNF did not result in any additional improvement in functional recovery. CONCLUSIONS: As neural grafting procedures in the nervous system evolve and genetically engineered cells or stem cells replace fetal tissue, crucial questions about cell number and trophic regulation will need to be addressed. This study demonstrates that grafting of 400,000 cells exposed to GDNF before transplantation has a beneficial effect in the restoration of complex sensorimotor behavior.

Adrenergic Agents↗
PubMed1997

Reconstruction of the striato-nigro-striatal circuitry by simultaneous double dopaminergic grafts: a tracer study using fluorogold and horseradish peroxidase.

The main strategy in neural transplantation for Parkinson's disease (PD) has been the ectopic placement of dopaminergic grafts in the striatum in order to restore dopaminergic innervation to the host striatum. Although intrastriatal transplants usually improve asymmetric rotational behavior in the 6-hydroxydopamine lesioned rodent model of PD, they are less likely to completely restore the more complex sensorimotor behavioral deficits induced by dopamine loss. Re-establishment of the nigrostriatal circuitry and dopaminergic reinnervation of the substantia nigra may be necessary to promote a more complete restoration of function in the dopamine depleted brain and improve the clinical efficacy of dopaminergic transplants. Recently, we demonstrated the reconstruction of the nigrostriatal pathway by simultaneous intrastriatal and intranigral dopaminergic transplants [Mendez et al., J. Neurosci. 16 (1996) 7216-7227.]. Using this strategy, it was found that placing a graft of embryonic ventral mesencephalic tissue in the striatum promoted the growth and guidance of axons from a similar graft placed homotopically in the ventral mesencephalon. Since it is apparent that developing tissue has the ability to promote axonal growth and guidance along the nigrostriatal pathway, the double grafting strategy may contribute to re-establishing host-graft connectivity. The current study provides evidence of reconstruction of the striato-nigro-striatal loop circuitry by simultaneous intrastriatal and intranigral dopaminergic transplants. Injection of the retrograde tracer fluorogold (FG) into the striatum resulted in fluorescent labeled cells within the intranigral grafts. Similarly injection of FG into the nigra resulted in fluorescent labeled cells within the intrastriatal graft and surrounding striatum. Injection of the anterograde tracer horseradish peroxidase (HRP) resulted in the presence of HRP reaction product throughout the target striatum. These results strongly support the re-establishment of nigrostriatal and striatonigral connections between simultaneous intrastriatal and intranigral dopaminergic transplants and suggest reconstruction of the striato-nigro-striatal loop circuitry.

Animals↗
PubMed1997

Neural transplantation in Parkinson's disease.

Parkinson's disease is a neurodegenerative disorder that affects about 1% of Canadians between the ages of fifty and seventy. The medical management for these patients consists of drug therapy that is initially effective but has limited long term benefits and does not alter the progressive course of the disease. The recalcitrance of longstanding Parkinson's disease to medical management has prompted the use of alternative surgical therapies. Many neurosurgical procedures have been utilized in order to improve the disabling symptoms these patients harbour. Although most of the current procedures involve making destructive lesions within various basal ganglia nuclei, neural transplantation attempts to reconstitute the normal nigrostriatal pathway and restore striatal dopamine. The initial success of neural transplantation in the rodent and primate parkinsonian models has led to its clinical application in the treatment of parkinsonian patients. Currently, well over one hundred patients throughout the world have been grafted with fetal tissue in an effort to ameliorate their parkinsonian symptoms. Although the results of neural transplantation in clinical trials are promising, a number of issues need to be resolved before this technology can become a standard treatment option. This review focuses on the current status of neural transplantation in Parkinson's disease within the context of other surgical therapies in current use.

Animals↗
PubMed1996

Reconstruction of the nigrostriatal pathway by simultaneous intrastriatal and intranigral dopaminergic transplants.

The main strategy in experimental and clinical neural transplantation in Parkinson's disease has been to place fetal nigral grafts not in their ontogenic site (substantia nigra) but in their target area (striatum). The reason for this ectopic placement is the apparent inability of nigral grafts placed in the ventral mesencephalon (VM) of the adult host to grow axons for long distances that are capable of reaching the ipsilateral striatum and thus restoring the nigrostriatal pathway. The present study demonstrates for the first time that simultaneous dopaminergic transplants (double grafts) placed in the substantia nigra and ipsilateral striatum of rats bearing unilateral 6-hydroxydopamine lesions reconstruct the dopaminergic nigrostriatal pathway in the adult rat brain. Numerous tyrosine hydroxylase-immunoreactive axons were observed arising from the intranigral graft and growing rostrally along the internal capsule and medial forebrain bundle to reinnervate the ipsilateral striatum, which also had received a dopaminergic graft. These double grafts achieved not only greater striatal reinnervation than the standard intrastriatal graft but also a faster and more complete rotational recovery to amphetamine challenge 6 weeks after transplantation. These results suggest strongly that embryonic nigral transplants implanted in the striatum are capable of promoting growth and providing guidance to axons arising from a dopaminergic graft placed homotopically in the VM, resulting in restoration of the dopaminergic nigrostriatal projection. Reconstruction of the nigrostriatal pathway by double grafts may not only achieve substantial striatal reinnervation but may also contribute to the reestablishment of dopaminergic regulation of the nigrostriatal circuitry.

Amphetamine↗
PubMed1996

Biosynthesis of cyclic diterpene hydrocarbons in rice cell suspensions: conversion of 9,10-syn-labda-8(17),13-dienyl diphosphate to 9beta-pimara-7,15-diene and stemar-13-ene.

The biosynthesis of diterpene hydrocarbons with enzyme extracts from rice cell suspension cultures was investigated to verify proposed pathways and intermediates in the production of the momilactone and oryzalexin phytoalexins. Diterpene synthase activity in cells treated with chitin to elicit the phytoalexin response was compared with the activity in untreated cells using the acyclic substrates [1-3H](E,E,E)- and [1-3H] (E,Z,E)-geranylgeranyl diphosphates (GGPPs 4-OPP and 11-OPP) as well as the bicyclic substrates [15-3H]ent-copalyl and [15-3H] syn-copalyl diphosphates (CPPs, 5-OPP, and 6-OPP). ent-kaurene (7), ent-sanda, racopimaradiene (8), 9 beta H-pimara-7,15-diene (9), and stemar-13-ene (10) were identified as major products by comparisons with authentic standards. Marked increases in diterpene synthase activities were observed with enzyme from chitin-treated cells: (E,E,E)-GGPP (approximately 100 fold), ent-CPP (approximately 3 fold), and syn-CPP (approximately 60 fold). The very low conversions of (E,Z,E)-GGPP to hydrocarbon products excludes its role in the biosynthesis of 9,10-syn-diterpenes in rice cells. ent-Kaurene was the major diterpene formed from ent-CPP with enzyme from unelicited cells. In contrast the enzyme from chitin-treated cells converted ent-CPP to a mixture of ent-kaurene, ent-sandaracopimaradiene, and a third unidentified diterpene. With syn-CPP as substrate the induced syntheses afforded a mixture of 9 beta-pimaradiene, stemarene, and a third, unidentified syn-diterpene. Overall the results are consistent with the hypothesis that rice cells respond to treatment with chitin fragments by producing new diterpene synthases not present in the untreated cells. These induced cyclases initiate phytoalexin biosynthesis by diverting (E,E,E)-GGPP into new cyclization modes that produce ent-sandaracopimaradiene, stemarene, and 9 beta-pimaradiene, the presumed precursors to oryzalexins A-F, oryzalexin S, and momilactones A-C, respectively. The intermediate role of 9,10-syn-CPP in syn diterpene biosynthesis is verified.

Biotransformation↗
PubMed1996

Frequency analysis of amino acids in the recognition regions of T-cell receptors.

In immunoglobulins (Igs), key amino acids in the Complementarity Determining Regions (CDR) are responsible for maintaining specific conformations called canonical structures. In T-cell receptors (TCRs), protein members of the Ig superfamily, the corresponding residues for maintaining these canonical structures have not been found. In previous studies we have found in Igs that the frequency of use of amino acids in some positions of the CDRs follows an inverse power law distribution, while the frequency of amino acids in the rest of the positions of the CDRs follows an exponential law distribution. The positions that follow the inverse power law distribution are precisely those involved in maintaining the canonical structures, while those positions for which the distribution fits the exponential distribution are those that should be properly involved in the recognition mechanism. In this paper, when the same analysis is applied to the use frequency of amino acids on the CDRs of TCRs, it is found that some positions that have been previously identified as having a structural role are those fitting the inverse power law. That finding combined with the cooperative or long-range interaction properties of systems that follow the inverse power law leads us to propose that the lack of determined key residues in certain positions is compensated by "equivalent' residues in other positions within the CDRs in order to maintain the canonical structures. Other positions that follow the exponential distribution are those which can be involved in the recognition process. These results coincide with a computer-generated model of TCR/peptide/MHC interaction previously published by the authors.

Amino Acid Sequence↗
PubMed1996

Sequence analysis of the V1-V2 hypervariable region of the HIV-1 envelope gene from pediatric patients.

The presence of HIV-1 DNA sequence variants of pediatric AIDS patients was investigated in a two-stage polymerase chain reaction (PCR) using nested primers for the first and second (V1-V2) hypervariable regions of the proviral envelope (gp 120) gene (env1). Gel electrophoresis analysis yielded amplified DNA bands which exhibited length variations which were characteristic for each child. The PCR products were cloned and the resulting clones demonstrated inserts of different lengths in a patient and between patients. Analysis of five clones from two different patients at the level of DNA sequencing indicates an extreme heterogeneity in the V1-V2 region. DNA maximum similarity between all of the isolated clones ranged between 69 to 96%. Comparison between DNA sequences of the isolated clones and HIV-1 strains of other parts of the world was also performed. The highest percentage of similarity that was found with known HIV variants included the following strains: HIVADA, HIVJFL, HIVSW42, HIVSWB83, HIVTRA2, HIVWMJ22. The sequences also showed a high degree of similarity to the clade B virus HIVSF162. The analyzed HIV-1 sequences demonstrated the expected high degree of variation in the V1-V2 region of the envelope gene and in some cases that the variation between isolates from the same patient may exceed the variation between the individual clones and the reference HIV-1 strains.

Amino Acid Sequence↗
PubMed1995

Epidemiology of canine leishmaniasis in the Madrid region, Spain.

A cross-sectional serological survey was carried out in the Madrid Autonomous Region (Comunidad de Madrid) in order to study and describe canine leishmaniasis epidemiology. The presence of leishmaniasis-specific antibodies was ascertained by immunofluorescence testing, 591 dogs were screened, revealing a prevalence of 5.25% (95% confidence interval 7.4-3.6), with no difference being encountered between rural and periurban areas. Age-specific prevalence exhibits a peak at 2-3 years and another at 7-8 years. Incidence or force of infection by occupation is as follows: pet dogs 0.059 (95% confidence interval 0.009-0.108) and working dogs 0.035 (95% confidence interval 0.012-0.057), there being a ratio between infection rates of 1.7, viz., indicating a 70% greater risk of infection among pet than among working dogs. The basic case reproduction number R0 is 1.06, suggesting that very intense control measures would not be needed for a drop in prevalence and incidence of infection to be achieved.

Age Factors↗
PubMed1993

GABAergic synaptic interactions in the substantia nigra.

The substantia nigra receives a strong GABAergic input from the ipsilateral striatum and globus pallidus. Nigral GABAergic synaptic interactions have been described in the pars compacta (SNC) and pars reticulata (SNR) but not in the pars lateralis (SNL). The SNR and particularly the SNL are the nodal points of the GABAergic nigrotectal pathway. The present study analyzes the synaptic connections of GABAergic and dopaminergic neurons in each of the divisions of the substantia nigra by employing a double-labeling immunocytochemical technique at the light and electron microscope levels. Glutamic acid decarboxylase (GAD)-containing terminals make symmetrical synaptic contacts with dopaminergic neurons in the SNC and SNR. Neurons that contain GAD also receive a GABAergic input in the SNR and SNL. The proportion of GAD-GAD contacts appears to be highest in the SNL where virtually all GAD-positive terminals are found to be in synaptic contact with or apposed to GAD positive profiles. This study demonstrates a strong GABAergic input onto nigral dopaminergic neurons and GABAergic neurons in the SNR and SNL. This GABAergic influence which is ostensibly striatal or pallidal in origin is particularly prominent in relation to the SNL-mediated nigro-collicular pathway.

Animals↗
PubMed1993

Investigation of an outbreak of Salmonella typhi in a public school in Madrid.

A typhoid fever outbreak affecting 54 school students occurred in a Public School of Móstoles, Madrid. The date of onset was 11 June 1991 and the last detected case was 8 July 1991. Salmonella typhi was cultured from blood and/or stool samples corresponding to 54 patients and one food-handler. There were no secondary cases detected. Epidemiological investigation suggested a salad or a custard as the common source. Patients and the food-handler were treated with ampicillin/amoxicillin for up to three weeks. There were seven relapses that were also treated with the same antibiotics with success. None were found to be excreting the organisms when tested after four months. All the Salmonella typhi isolated strains were phagetype 34, biotype Xylose +, Tetrationate Reductase + and harboured a similar 22 Mdal plasmid, they were also susceptible to the antibiotics tested.

Adolescent↗
PubMed1992

Substance P synaptic interactions with GABAergic and dopaminergic neurons in rat substantia nigra: an ultrastructural double-labeling immunocytochemical study.

The distribution of substance P (SP), tyrosine hydroxylase (TH), and glutamic acid decarboxylase (GAD) immunoreactivity in the substantia nigra of the rat was studied by means of an ultrastructural double-labeling immunocytochemical method. Direct synaptic contact between SP-immunoreactive terminals and GAD-positive nigral neurons was more often observed in the pars lateralis than the pars reticularis and was rarely observed in the pars compacta. Substance P-positive terminals also formed synapses with cell bodies and dendrites of TH-positive, dopaminergic neurons in the pars compacta and pars reticulata. Multiple SP-immunoreactive terminals were often observed with symmetrical and, less frequently, asymmetrical synapses on individual TH-containing dendrites. Evidence of SP-containing terminals contacting both GABAergic and dopaminergic neurons in the substantia nigra suggests a direct excitatory action upon nigral projection neurons.

Animals↗
PubMed1991

Dopaminergic innervation of substance P-containing striatal neurons by fetal nigral grafts: an ultrastructural double-labeling immunocytochemical study.

Evidence for survival and growth of fetal substantia nigra grafts in host striatum and partial reversal of behavioural and biochemical deficits in the host animal is well documented. Afferent synaptic connections arising from the graft and contacting host structures have also been reported; however, the properties of the neurons receiving this input is less clear. The purpose of this study was to determine if substance P-containing neostriatal neurons receive a dopaminergic input from nigral grafts. Fetal substantia nigra cell suspensions were stereotaxically implanted in the deafferented neostriatum of Wistar rats 2 weeks after a unilateral 6-hydroxydopamine (6-OHDA) lesion in the ipsilateral substantia nigra or medial forebrain bundle. The ultrastructural features of the graft-host synaptic interactions were analysed by employing an electron microscope immunocytochemical double-labeling technique. Tyrosine hydroxylase (TH) and substance P-immunoreactive structures were simultaneously demonstrated by means of the peroxidase-antiperoxidase method using two different chromogens with distinct reaction products easily differentiated at the light and electron microscope levels. TH-immunoreactive sites were first demonstrated using 3,3'-diaminobenzidine tetrahydrochloride (DAB); then substance P immunoreactivity was localized using benzidine dihydrochloride (BDHC). TH-immunoreactive terminals of axons originating from the graft made synaptic contacts with substance P-positive cell bodies and dendrites from the host. These results indicate that at least partial restoration of the normal nigrostriatal circuitry can be achieved following nigral grafts. The demonstration of specific synaptic input on host substance P neurons provides an anatomical basis for direct functional modulation of the deafferented host neostriatum by the nigral graft.

Animals↗
PubMed1987

Serum lipids after stroke.

To ascertain the appropriate time for detecting lipid abnormalities for prophylaxis, serial analyses of fasting serum lipoproteins were undertaken prospectively in men with cerebral infarction or transient ischemic attacks. Serum total cholesterol (T CHOL) and low density lipoprotein cholesterol (LDL CHOL) in cerebral infarction patients aged 50 to 69 were lowest on day 7, intermediate on day 1, and highest at 3 months, whereas very low density lipoprotein and high density lipoprotein cholesterol (HDL CHOL) changed little. The day 1 mean fasting serum HDL CHOL of cerebral infarct patients was significantly lower in subjects aged 50 to 59 than in those aged 60 to 69 (23 +/- 3 versus 42 +/- 5 mg/dl), and there was a corresponding higher ratio of T CHOL:HDL CHOL (12.7 +/- 4.5 versus 4.7 +/- 0.4, p less than 0.01). Mean HDL CHOL levels were low normal to low in patients aged 50 to 69 with transient ischemic attacks. Both serum cholesterol and triglyceride levels are initially decreased in patients aged 50 to 69 with cerebral infarction, whereas only cholesterol is decreased in patients 60 to 69 with transient ischemic attacks. Important lipoprotein abnormalities may be missed in the acute phase.

Aged↗
PubMed1985

Serum enzymatic changes following infection of mice with Mycobacterium lepraemurium.

Mice injected interperitoneally with 1.5 X 10(8) Mycobacterium lepraemurium develop progressive visceral alterations that are reflected in the lactic dehydrogenase (LDH), glutamate-pyruvate transaminase (GPT), and glutamate-oxalacetate transaminase (GOT) levels. The rise in GPT and GOT levels starts earlier (about 30 days post-infection) than the rise in LDH activity (about 70 days), but the latter shows the most impressive increases. Differences between infected and control groups, however, reach statistical significance only at 75 days (LDH), 90 days (GOT), and 150 days (GPT) post-inoculation, still well before the appearance of obvious external signs of infection (about 240 days in our model). It is suggested that the ratio of enzyme levels in infected to enzyme levels in uninfected animals could be taken as a reliable index to follow the progress of the infection with M. lepraemurium.

Alanine Transaminase↗