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Biomedical subjects

M Rodriguez

Publications and source records attributed to M Rodriguez.

At least 397 records · Page 22Linked to original sources
PubMed1994

Motor response to apomorphine and levodopa in asymmetric Parkinson's disease.

The motor responses of 14 patients with Parkinson's disease (six previously untreated and eight chronically receiving levodopa) with pronounced asymmetry in the severity of motor signs between the left and right sides of the body were studied. The effects of a short (60 minutes) and a long (16-22 hours) intravenous levodopa infusion as well as of subcutaneous apomorphine (1-6 mg bolus) were assessed. Four different tapping tests were used to measure motor function. For all pharmacological tests, the more affected side showed a shorter response duration, increased latency, and greater response magnitude than the less affected side. These differences were more pronounced in those patients receiving chronic levodopa treatment. As apomorphine is not dependent on dopamine storage capacity, these findings suggest that postsynaptic mechanisms play an important part in the origin of motor fluctuations in Parkinson's disease.

Apomorphine↗
PubMed1994

Intravenous immunoglobulin therapy in multiple sclerosis: progress from remyelination in the Theiler's virus model to a randomised, double-blind, placebo-controlled clinical trial.

No treatment has been found which reverses long-standing neurological dysfunction in patients with multiple sclerosis (MS). Observations in animal models of MS show that immunoglobulins directed against CNS components promote oligodendroglial proliferation and new myelin synthesis. Preliminary studies in inflammatory-demyelinating diseases of the human peripheral and central nervous system suggest that the repeated intravenous administration of polyclonal human immunoglobulin (IVIg) is sometimes followed by clinical improvement. A randomised, placebo-controlled, double-blind, clinical trial was designed to test the hypothesis that repeated administration of IVIg will result in a meaningful degree of recovery of apparently irreversibly lost neurological function (weakness). A total of 76 patients with MS will participate in the study. These patients had developed a fixed, apparently permanent weakness that had not improved in the preceding four to 18 months. If effective, IVIg administration may benefit the large proportion of patients with MS who have active disease by enhancing the potential for myelin repair in the evolution of the inflammatory-demyelinating lesion.

Animals↗
PubMed1994

Promotion of remyelination by polyclonal immunoglobulin in Theiler's virus-induced demyelination and in multiple sclerosis.

Spontaneous remyelination occurs in experimental models of demyelination and in patients with multiple sclerosis, although to a limited extent. This enables the search for factors that promote remyelination. Using the Theiler's virus model of central nervous system demyelination, promotion of remyelination was observed after passive transfer of CNS-specific antiserum and transfer of CNS-specific purified immunoglobulin. Mouse polyclonal immunoglobulin from normal non-syngeneic mice, comparable with the human immunoglobulin preparation, also promotes CNS remyelination in the Theiler's virus model of multiple sclerosis. These experimental findings further bridge the gap with a pilot study that suggests clinical improvement after polyclonal immunoglobulin administration, possibly due to remyelination, in some multiple sclerosis patients with stable, steroid-unresponsive optic neuritis. In view of these experimental and clinical data, the physiological role of myelin in demyelination and remyelination is discussed, and the role of IgG solely as a deleterious molecule in the pathophysiology of multiple sclerosis and experimental demyelination is addressed.

Animals↗
PubMed1994

Impairment, disability, and handicap in multiple sclerosis: a population-based study in Olmsted County, Minnesota.

We studied functional status of MS patients in a geographically based cohort in Olmsted County, Minnesota. The 162 definite MS patients who were alive and residing in the study area on December 1, 1991, constituted the MS prevalence disability cohort. We identified 179 cases of definite or probable MS, providing an overall sex- and age-adjusted prevalence rate of 167.5 per 100,000. Median duration of MS from onset was 15.4 years, and median age on prevalence date was 47.5 years. The Minimal Record of Disability for MS determined the degree of impairment, disability, and handicap of the entire cohort within 4 months of the prevalence date. The frequency of Expanded Disability Status Scale scores of the MS prevalence cohort showed a bimodal distribution with peaks at 1 and 6.5 (3.5 [1 to 9.5], median [range]). Approximately one-third of the cohort had marked paraparesis, paraplegia, or quadriplegia. One-fourth of all patients needed intermittent or almost constant catheterization for bladder dysfunction. Few patients (3.7%) reported severe decrease in mentation or dementia requiring supervision. Many patients (53.1%) were working full-time. Most patients (72.2%) maintained their usual financial standard without external support. There were no differences in level of impairment, disability, or handicap observed between the subgroup of 122 patients (75.3%) who are incident cases (onset of disease as residents of Olmsted County) compared with the entire prevalence cohort. This geographically based study of MS demonstrates that the functional status is more favorable than previously recognized.

Activities of Daily Living↗
PubMed1994

Influence of deletion of T cell receptor V beta genes on the Theiler's virus model of multiple sclerosis.

To determine the role of TCR V beta genes in a model of multiple sclerosis (MS), we studied Theiler's virus infection in congenic mice with deletion of TCR V beta chromosome. Congenic mice expressing the V beta a [50% deletion of TCR V beta] or V beta c 70% deletion of TCR V beta] haplotype were generated in mice resistant [B10 (H-2b)], intermediate [B10.K (H-2k), B10.RIII (H-2r)] or susceptible [B10.S (H-2s), and B10.Q (H-2q)] to Theiler's virus induced demyelination. Deletion of TCR V beta genes (V beta a or V beta c) did not convert B10 or B10.K congenic mice to susceptibility. In contrast, congenic B10.RIII-V beta c developed prominent demyelination and 10- to 100-fold increase in virus-antigen expression in spinal cord compared to B10.RIII mice. No effect on the extent of demyelination was observed in B10.S-V beta a, B10.S-V beta c or B10.Q-V beta c mice. These experiments illustrate the critical interactions between MHC, TCR, and background genes in susceptibility to immune-mediated disease.

Animals↗
PubMed1994

Epidemic cholera in Trujillo, Peru 1992: utility of a clinical case definition and shift in Vibrio cholerae O1 serotype.

Epidemic cholera continues in Peru. Since 1991, cholera surveillance in Peru has been based mainly on clinical recognition. To determine the proportion of reported cholera patients who actually have cholera and to evaluate the clinical case definition used in surveillance, we cultured rectal swabs from patients presenting with acute diarrhea in March 1992 in Trujillo, Peru. Of 197 patients meeting the clinical case definition, 174 (88%) had confirmed Vibrio cholerae O1 infection. In this epidemic setting, watery diarrhea of sudden onset in a person of any age presenting for treatment is highly predictive of cholera. Of note, 90% of the current V. cholerae O1 El Tor isolates were of serotype Ogawa, while a year earlier, all were of serotype Inaba.

Acute Disease↗
PubMed1994

Left ventricular function determined by Doppler echocardiography in adolescents with type I (insulin-dependent) diabetes mellitus.

Sixty-one children with insulin-dependent diabetes mellitus and twenty-three healthy subjects were investigated. The patients with diabetes mellitus aged 4 to 20 years (13.4 +/- 4.0) had had diabetes for 1 to 16 years (6.4 +/- 3.5). There were no cardiovascular risk factor other than diabetes. Patients received no medication other than insulin. The following echocardiographic and Doppler parameters of the left ventricle were analyzed in both groups: systolic and diastolic dimensions, systolic time intervals, fractional shortening, mean velocity of circumferential fiber shortening, percent relaxation of the left ventricular posterior wall at 50% of diastole, peak velocity of early (E) and late atrial (A) mitral flow. E/A ratio, deceleration of the E-wave, and the isovolumetric relaxation time. None of the parameters were significantly different between the groups. There was no relation observed between duration of diabetes and any of the parameters analyzed. It is concluded that there is not echocardiographic data to support the concept of diabetic cardiomyopathy in adolescents with type I (insulin-dependent) diabetes mellitus.

Adolescent↗
PubMed1994

[Cerebral abscesses. The clinical and evolutionary aspects of 17 cases treated surgically].

Seventeen cases of cerebral abscesses undergoing surgery were reviewed, underlying the characteristics of predisposing factors, infectious sources, microbiological and radiological studies, as well as clinical and evolutive aspects. The average age of the patients was 34 years, with a higher incidence in the second (35%) and sixth (22%) decades. The young patients (< 40 years) showed a greater frequency of adjacent infectious sources (83%) and the older patients (> 40 years), distant infectious sources (75%). The average time gap between the onset of symptoms and the diagnosis was 7 +/- 13 days. CAT showed in all the patients typical hypodense images with a peripheral ring; three patients had multiple abscesses and the remainder, single abscesses. In 12 patients (70.5%), microbiological cultures were positive, 3 (25%) for aerobe germs, 7 (50.3%) for anaerobe germs, 1 (8.33%) for multiple germs and 1 (8.33%) for fungi. Eleven patients underwent surgical drainage, four of which required latter exeresis. Six other patients underwent exeresis as the only surgical treatment. One patient died and the remainder showed a positive evolution. The hospital length of stay was 42.3 +/- 52.3 days. The most frequent sequela was the epilepsia present in 23.5% of the patients. Our findings are similar to the results of recent works, although in our series, there is a higher frequency of anaerobe germs. No differences were observed between the surgical techniques used nor between the past and current antibiotherapy patterns.

Adolescent↗
PubMed1994

Monoclonal autoantibodies promote central nervous system repair in an animal model of multiple sclerosis.

Susceptible strains of mice infected intracerebrally with Theiler's murine encephalomyelitis virus develop a chronic, progressive, immune-mediated CNS demyelinating disease similar both pathologically and clinically to multiple sclerosis. Previous reports indicated that polyclonal immunoglobulins from mice injected with homogenized spinal cord promote CNS remyelination when given to SJL/J mice chronically infected with Theiler's virus. To explore further both the mechanism(s) and potential therapeutic usefulness of antibodies in the treatment of CNS demyelinating diseases, we made a panel of monoclonal antibodies derived from splenocytes of SJL/J mice injected with homogenized spinal cord, and screened them for their autoantigen-binding capability. Monoclonal IgM autoantibodies from two clones, designated SCH94.03 and SCH94.32, promoted fourfold more CNS remyelination than controls when given to chronically infected SJL/J mice. CNS remyelination, assessed morphologically by the presence of abnormally thin myelin sheaths relative to axonal diameter, correlated with the absence of clinical disease progression. In titration experiments, treatment with SCH94.03 and remyelination had a positive dose-response relationship, and as little as 10 micrograms of antibody promoted remyelination. Both SCH94.03 and SCH94.32 showed multiorgan autoreactivity, and recognized both surface and cytoplasmic determinants on glial cells. We propose that this model provides a unique system to elucidate the mechanism(s) and test the reparative potential of autoantibodies in the treatment of CNS injury.

Animals↗
PubMed1994

Frequency of sister chromatid exchanges in humans at 14-16 week foetal stage and at birth.

In order to identify transplacental induced mutagenicity in humans the baseline frequency of sister chromatid exchanges (SCEs) in amniotic fluid cells (8.56 +/- 0.28 per cell) from 14 to 16-week-old foetuses as well as in peripheral blood lymphocytes (7.96 +/- 0.26 per cell) from newborns was determined. A group of twelve patients who were analysed both at 14-16 weeks gestation and at birth showed no SCE variations. These results suggest that foetal amniocytes and T lymphocytes from newborns present a similar sensitivity to the mutagenic activity of the thymidine analogue 5-bromodeoxyuridine employed in the sister chromatid differentiation.

Adult↗
PubMed1993

Spontaneous firing of nigrostriatal dopaminergic neurons in split-brain rats.

The regulatory action of the contralateral brain side on nigrostriatal dopaminergic (NSDA) neurons was examined in anesthetized rats using extracellular single-unit recording techniques. The spontaneous activity of NSDA cells was recorded from split-brain, sham-lesioned or intact-brain rats. The three groups of cells did not differ in antidromic latency and firing rate. However, cells from split-brain rats exhibited a more regular pattern of discharge than those recorded in the two control groups as shown by autocorrelograms and the standard deviation and variation coefficient of the interspike intervals. In addition, burst firing was found to be markedly reduced in the split-brain group. It is concluded that decussating pathways are involved in the regulation of the discharge pattern of NSDA neurons.

Action Potentials↗
PubMed1993

Synthesis and biological evaluation of cholecystokinin analogs in which the Asp-Phe-NH2 moiety has been replaced by a 3-amino-7-phenylheptanoic acid or a 3-amino-6-(phenyloxy)hexanoic acid.

Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-Asp-2-phenylethyl ester (JMV180), an analog of the C-terminal octapeptide of cholecystokinin (CCK-8), shows interesting biological activities behaving as an agonist at the high-affinity CCK binding sites and as an antagonist at the low-affinity CCK binding sites in rat pancreatic acini. Although we did not observe any major hydrolysis of the ester bond of Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-Asp-2-phenylethyl ester in our in vitro studies, we were aware of a possible and rapid cleavage of this ester bond during in vivo studies. To improve the stability of Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-Asp-2-phenylethyl ester, we decided to synthesize analogs in which the ester bond would be replaced by a carba (CH2-CH2) linkage. We synthesized the 3-amino-7-phenylheptanoic acid (beta-homo-Aph) with the R configuration in order to mimic the Asp-2-phenylethyl ester moiety and the 3-amino-6-(phenyloxy)hexanoic acid (H-beta-homo-App-OH), an analog of H-beta-homo-Aph-OH in which a methylene group has been replaced by an oxygen. (R)-beta-Homo-Aph and (R)-H-beta-homo-App-OH were introduced in the CCK-8 sequence to produce Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-(R)-beta-homo-Aph-OH and Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-(R)-beta-homo-App-OH. Both compounds were able to recognize the CCK receptor on rat pancreatic acini (IC50 = 12 +/- 8 nM and 13 +/- 5 nM, respectively), on brain membranes (IC50 = 32 +/- 2 nM and 57 +/- 5 nM, respectively), and on Jurkat T cells (IC50 = 75 +/- 15 nM and 65 +/- 21 nM, respectively). Like Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-Asp-2-phenylethyl ester, both compounds produced maximal stimulation of amylase secretion (EC50 = 6 +/- 2 nM and 4 +/- 2 nM, respectively) with no decrease of the secretion at high concentration indicating that these compounds probably act as agonists at the high-affinity peripheral CCK-receptor and as antagonists at the low-affinity CCK-receptor. Replacing the tryptophan by a D-tryptophan in such analogs produced full CCK-receptor antagonists. All these analogs might be more suitable for in vivo studies than Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-Asp-2-phenylethyl ester.

Amino Acid Sequence↗
PubMed1993

Differential expression of H-2K and H-2D in the central nervous system of mice infected with Theiler's virus.

A model of demyelination induced by Theiler's murine encephalomyelitis virus (TMEV) was used to study differential regulation of class I MHC gene products in the brain and spinal cord of resistant (B10) and susceptible (B10.Q and B10.RBQ) mice. Allelic polymorphisms in the H-2D region, but not the H-2K region, play a primary role in determining susceptibility to late demyelinating disease. However, even though significant structural diversity distinguishes class I alleles, there are no discernible K or D-specific patterns of structural diversity within the peptide binding domains of these glycoproteins. Our hypothesis was that D region association of susceptibility to demyelination was related to differences in the expression of the K and D Ag in the central nervous system (CNS) after TMEV infection. Using allele-specific mAb and an immunoperoxidase technique, we demonstrated transient but equivalent increases in K and D Ag expression in the brain and spinal cord of resistant mice beginning 7 days after TMEV infection, which returned to baseline by 90 days. However, when genetically susceptible animals were examined, a significantly greater increase in D expression relative to K expression was seen in the brain and spinal cord at all post-infection observation periods. Immunosuppression of genetically resistant animals before TMEV infection, which results in viral persistence, was accompanied by equivalent increases in both the K and D Ag. Depletion of CD8+ T cells, but not CD4+ T cells, in susceptible mice ablated class I expression in the CNS in response to TMEV infection, implying that CD8+ cells contribute to the differential regulation of K and D Ag in the CNS. These findings are consistent with the hypothesis that differences in gene regulation may account for different roles of the K and D loci play in determining resistance and susceptibility to TMEV-induced demyelinating disease.

Animals↗