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Biomedical subjects

M Rodriguez

Publications and source records attributed to M Rodriguez.

At least 19 recordsLinked to original sources
PubMed1992

JMV 449: a pseudopeptide analogue of neurotensin-(8-13) with highly potent and long-lasting hypothermic and analgesic effects in the mouse.

We recently reported that H-Lys psi (CH2NH)Lys-Pro-Tyr-Ile-Leu-OH (JMV 449), a pseudopeptide analogue of neurotensin-(8-13) with a reduced CH2NH bond in position 8-9, was about 3 times more potent than neurotensin in binding to mouse brain membranes and in contracting the guinea-pig ileum, and was markedly more resistant to degradation than neurotensin when exposed to rat brain membranes. In the present study, we compared the time courses and dose-response relationships for the ability of i.c.v. injected neurotensin and JMV 449 to elicit hypothermia and analgesia (tail-flick test) in the mouse. The results show that the pseudopeptide analogue behaved as a highly potent and long-lasting neurotensin agonist in these two in vivo bioassays. The analogue should prove very useful for studying the effects of chronic neurotensin receptor stimulation in vitro and in vivo.

Amino Acid Sequence↗
PubMed1992

Effects of thiorphan, bestatin and a novel metallopeptidase inhibitor JMV 390-1 on the recovery of neurotensin and neuromedin N released from mouse hypothalamus.

The effects of the endopeptidase 24.11 ('enkephalinase') inhibitor thiorphan, the aminopeptidase inhibitor bestatin and a novel metallopeptidase inhibitor JMV 390-1 on the K(+)-evoked release of immunoreactive neurotensin and neuromedin N (iNT and iNN) from mouse hypothalamic slices were examined. (JMV 390-1 inhibits several metallopeptidases including endopeptidases 24.11, 24.15 and 24.16, and aminopeptidase N equipotently with Ki values around 50 nM.) Thiorphan increased the recovery of released iNT nearly 2-fold and had no effect on iNN. Bestatin produced a 4-fold increase in iNN recovery and was inactive on iNT. Finally, iNT and iNN recoveries were increased up to 4- and 5-fold, respectively, by JMV 390-1. These results show that in the mouse hypothalamus endopeptidase 24.11 participates with other metalloendopeptidases to the degradation of endogenously released NT while endogenously released NN is principally degraded by aminopeptidase(s).

Amino Acid Sequence↗
PubMed1992

Waterborne transmission of epidemic cholera in Trujillo, Peru: lessons for a continent at risk.

The epidemic of cholera that began in Peru in January, 1991, marked the first such epidemic in South America this century. Subsequently, over 533,000 cases and 4700 deaths have been reported from nineteen countries in that hemisphere. We investigated the epidemic in Trujillo, the second largest city in Peru. Trujillo's water supply was unchlorinated and water contamination was common. Suspect cholera cases were defined as persons presenting to a health facility with acute diarrhoea between Feb 1, and March 31, 1991. We studied a cohort of 150 patients who had been admitted to hospital and conducted a matched case-control study with 46 cases and 65 symptom-free and serologically uninfected controls; we also carried out a water quality study. By March 31, 1991, 16,400 cases of suspected cholera (attack rate 2.6%), 6673 hospital admissions, and 71 deaths (case-fatality rate 0.4%) had been reported in the province of Trujillo. 79% of stool cultures of patients with diarrhoea presenting to a single hospital yielded Vibrio cholerae O1. In the case-control study, drinking unboiled water (odds ratio [OR] 3.1, 95% confidence interval [CI] 1.3-7.3), drinking water from a household water storage container in which hands had been introduced into the water (4.2, 1.2-14.9), and going to a fiesta (social event) (3.6, 1.1-11.1) were associated with illness. The water quality study showed progressive contamination during distribution and storage in the home: faecal coliform counts were highest in water from household storage containers and lowest in city well water. V cholerae O1, biotype El Tor, serotype Inaba, was isolated from three city water samples. Cholera control measures in Trujillo should focus on treatment of water and prevention of contamination during distribution and in the home. Trujillo's water and sanitation problems are common in South America; similar control measures are needed throughout the continent to prevent spread of epidemic cholera.

Adolescent↗
PubMed1992

NADH-activated cell-free transfer between Golgi apparatus and plasma membranes of rat liver.

This report concerns development of a cell-free system from rat liver to study transport of membrane constituents from the Golgi apparatus to the plasma membrane. Highly purified Golgi apparatus as donor and a mixture of sheets and vesicles as plasma membrane acceptor fractions were combined to analyze requirements for lipid and protein transport. In the reconstituted system, the Golgi apparatus donor was in suspension. To measure transfer, membrane constituents of the donor membranes were radiolabeled with [3H]acetate (lipids) or [3H]leucine (proteins). The plasma membrane vesicles were used as the acceptor and were unlabeled and immobilized on nitrocellulose for ease of recovery and analysis. The reconstituted cell-free transfer was dependent on temperature, but even at 37 degrees C, the amount of transfer did not increase with added ATP, was not specific for any particular membrane fraction or subfraction nor was it facilitated by cytosol. ATP was without effect both in the presence or absence of a cytosolic fraction capable of the support of cell-free transfer in other systems. In contrast to results with ATP, NADH added to the reconstituted system resulted in an increased amount of transfer. A further increase in transfer was obtained with NADH plus a mixture of ascorbate and dehydroascorbate to generate ascorbate free radical. The transfer of labeled membrane constituents from the Golgi apparatus to the plasma membrane supported by NADH plus ascorbate radical was stimulated by a cytosol fraction enriched in less than 10 kDa components. This was without effect in the absence of NADH/ascorbate radical or with ATP as the energy source. Specific transfer was inhibited by both N-ethylmaleimide and GTP gamma S. The findings point to the possibility of redox activities associated with the trans region of the Golgi apparatus as potentially involved in the transport of membrane vesicles from the Golgi apparatus to the cytoplasmic surface of the plasma membrane.

Animals↗
PubMed1992

Role of T cell receptor V beta genes in Theiler's virus-induced demyelination of mice.

Intracerebral infection of certain strains of mice with Theiler's virus results in chronic immune-mediated demyelination in spinal cord. We used mouse mutants with deletion of the V beta class of TCR genes to examine the role of TCR genes in this demyelinating disease which is similar to multiple sclerosis. Quantitative analysis of spinal cord lesions demonstrated a markedly increased number and extent of demyelinated lesions in persistently infected RIII S/J mice which have a massive deletion of the TCR V beta-chain (V beta 5.2, V beta 8.3, V beta 5.1, V beta 8.2, V beta 5.3, V beta 8.1, V beta 13, V beta 12, V beta 11, V beta 9, V beta 6, V beta 15, V beta 17) compared with B10.RIII mice which are of identical MHC haplotype (H-2r) but have normal complement of V beta TCR genes. In contrast, infection of C57L (H-2b) or C57BR (H-2k) mice which have deletion of the V beta TCR genes (V beta 5.2, V beta 8.3, V beta 5.1, V beta 8.2, V beta 5.3, V beta 8.1, V beta 13, V beta 12, V beta 11, and V beta 9) resulted in few demyelinating lesions. Genetic segregation analysis of (B10.RIII x RIII S/J) x RIII S/J backcrossed mice and (B10.RIII x RIII S/J) F2 mice demonstrated correlation of increased susceptibility to demyelination with deletion of TCR V beta genes. The increase in number of demyelinating lesions correlated with increase in number of virus-Ag+ cells in spinal cord. These experiments provide strong evidence that the structural diversity at the TCR beta-complex can influence susceptibility to virus-induced demyelination.

Animals↗
PubMed1992

The major Thiobacillus ferrooxidans outer membrane protein forms low conductance ion channels in planar lipid bilayers.

A protein isolated and purified from the outer membrane of the acidophilic, chemolithotrophic bacterium, Thiobacillus ferrooxidans with an oligomeric molecular weight of 90,000 Da (p90) was incorporated into phosphatidylethanolamine planar lipid bilayers. The protein formed slightly anionic channels in KCl solutions, with a conductance of 25 pS in 100 mM KCl. The current-voltage relationship was linear between +/- 60 mV, and the conductance was a saturating function of the salt concentration. These channels fluctuated from a single open to closed state at low potentials, but present flickering activity at higher potentials.

Bacterial Outer Membrane Proteins↗
PubMed1992

Multifocal inflammatory leukoencephalopathy with 5-fluorouracil and levamisole.

A cerebral demyelinating disease developed in 3 patients during adjuvant therapy with 5-fluorouracil and levamisole for adenocarcinoma of the colon. None of the patients had evidence of metastatic disease or prior neurological disease. The duration of chemotherapy before onset of neurological symptoms ranged from 15 to 19 weeks. The total dose of 5-fluorouracil was 9.7 to 15.7 gm. The total dose of levamisole was 2.7 to 3.75 gm. Two patients presented with a subacute (2-3 weeks) progressive decline in mental status and ataxia. The third patient had two unexplained episodes of loss of consciousness. In each, magnetic resonance imaging with gadolinium demonstrated prominent multifocal enhancing white matter lesions. Cerebral biopsy was performed stereotaxically in 2 patients. The morphological features were those of active demyelinating disease. The myelin loss was associated with numerous dispersed as well as vasocentric macrophages, sparing of axons, and perivascular lymphocytic inflammation. Electron microscopy confirmed the light microscopic findings. All 3 patients improved after cessation of chemotherapy and a short course of corticosteroid therapy. Our patients represent the first reported examples of an inflammatory leukoencephalopathy associated with the administration of 5-fluorouracil and levamisole. This syndrome may represent the pathological basis for 5-fluorouracil neurotoxicity, although we cannot completely exclude the role of levamisole.

Adenocarcinoma↗
PubMed1992

Revised estimate of the prevalence of multiple sclerosis in the United States.

Using three adjustments, we have revised a 1976 prevalence count for multiple sclerosis in the United States. The adjustments were made to data from a US national survey; they used 1990 population projections from the US Bureau of the Census, and results of investigations conducted in Weld and Larimer Countries, Colorado, and Olmsted County, Minnesota. It is estimated that approximately 250,000 to 350,000 persons in the United States in 1990 had physician-diagnosed multiple sclerosis.

Age Factors↗
PubMed1992

Prediction of severe coronary artery disease using computerized ECG measurements and discriminant function analysis.

This study tested the hypothesis that discriminant function analysis of clinical and exercise-test variables including computerized ST measurements could improve the prediction of severe coronary artery disease. Secondary objectives were to demonstrate the effect of digoxin and/or resting electrocardiographic (ECG) abnormalities, and to evaluate the relative importance of ST measurements made during the recovery phase and in the three lead group areas. The design was a retrospective analysis of data collected during exercise testing and coronary angiography. The ECG data were gathered and stored in digital format on optical discs and all ST measurements were made off-line using the authors' own software. Univariate and multivariate analytic methods were used to analyze all pretest characteristics as well as hemodynamic and computerized ECG responses to exercise. A 1,000-bed Veterans Affairs Medical Center served as the setting. The study included 446 male veterans who underwent a sign or symptom limited treadmill exercise test and coronary angiography. Analysis was also performed on a subset of this population formed by excluding patients receiving digoxin or with resting ECGs exhibiting left ventricular hypertrophy or ST depression (n = 328). In the total study population, the authors derived a treadmill score using discriminant function analysis. This score included: (1) the time-slope area in lead V5 during recovery; (2) delta heart rate; (3) angina pectoris during the exercise test; and (4) presence of diagnostic Q waves on the resting ECG. This score was effective in predicting triple vessel/left main disease and outperformed exercise-induced ST depression for predicting severe coronary artery disease. After exclusion of patients with ECGs exhibiting left ventricular hypertrophy or resting ST depression and patients receiving digoxin, discriminant function analysis chose: (1) the time-slope area in lead V5 during recovery and (2) delta heart rate. Exclusion of these patients resulted in a nonsignificant decrease in specificity of all ST criteria. ST-segment amplitude or slope in lead V5 at 3.5 minutes in recovery clearly outperformed the maximal exercise measurements in both groups. Summing the depressions or selecting the most depression in the three areas (ie, lateral-V5, inferior-II, anterior-V2) did not improve test performance. Leads other than V5 did not contain significant diagnostic information. A quantitative approach to exercise testing using discriminant function analysis enhanced the tests' performance for predicting severe coronary disease. The inclusion of patients taking digoxin or with resting ECG abnormalities nonsignificantly decreases the specificity of all ST criteria.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1992

An improved method for carotid artery infusion without vessel occlusion.

This is an simple, non-time-consuming and advantageous procedure for catheterization and drug administration in thin arteries of small animals. The cannulation method consists of implanting polyimide-coated silica capillary tubing. To avoid vascular tear during puncture, the tubing tip is beveled. The cannula is stuck to the wall of the artery without artery ligation, using a small drop of a fast cyanoacrylate adhesive. The surgical procedure can be completed in 15 min and has the following properties: 1) it is wise but not indispensable to perfuse a solution continually through the cannula; 2) the dead volume is low and drugs may be injected in a very low solution volume; 3) it is not necessary to close the lumen of the vessel during catheterization; 4) the drug solution may be perfused into a normal bloodstream and thus its kinetic behavior is not modified by undesired cul-de-sac effects presented after artery ligation.

Animals↗
PubMed1992

Human anti-F(ab')2 antibodies show preferential reactivity for F(ab')2 molecules bearing lambda light chains.

In order to evaluate binding specificities of anti-F(ab')2 antibodies from patients with systemic lupus erythematosus (SLE) and from normal healthy controls, F(ab')2 fragments were prepared from 24 IgG myelomas with defined isoelectric points, DNA-associated idiotypes, and kappa/lambda light chain types. Using ELISA and hemagglutination assays, anti-F(ab')2 antibodies from 12 healthy controls and 29 SLE patients were observed to exhibit preferential binding (lambda > kappa) to myeloma F(ab')2 fragments composed of lambda light chains (P < 0.0001). No correlation of anti-F(ab')2 binding and presence of cationic, neutral, or anionic isoelectric points or for DNA-associated idiotypes on monoclonal F(ab')2 was detected. Anti-F(ab')2 antibodies, often elevated in SLE during remission, show preferential specificity for F(ab')2 fragments bearing lambda light chains.

Adult↗
PubMed1992

Central nervous system demyelination and remyelination in multiple sclerosis and viral models of disease.

The mechanisms of myelin injury and repair were studied in acute multiple sclerosis lesions and in a murine model of demyelination induced by a virus. Injury to oligodendrocytes resulting in degeneration of inner glial loops and inner myelin lamellae (dying-back oligodendrogliopathy) was observed by electron microscopy in brain biopsies of acute demyelinating lesions. Attempts at central nervous system remyelination as manifested by thinly myelinated axons and proliferation of oligodendrocytes were observed at the edge of many acute plaques. To develop therapeutic strategies to inhibit demyelination or promote remyelination, mice infected intracranially with Theiler's virus (a picornavirus) were studied. Experimental manipulation of Theiler's virus-infected mice by treatment during chronic demyelinating disease with immunoglobulins directed at normal spinal cord antigens or with monoclonal antibodies which deplete CD4 or CD8-positive T cells resulted in augmentation of new myelin synthesis. These observations suggest that disturbances in the myelinating function of oligodendrocytes, events not accompanied by death of these cells, may be among the earliest pathological events in multiple sclerosis. Experiments using the Theiler's virus model of demyelination indicate that manipulation of the immune response has the potential to promote central nervous system remyelination and functional recovery in multiple sclerosis.

Animals↗
PubMed1992

Dopaminergic neuron development in rats: biochemical study from prenatal life to adulthood.

Dopaminergic cell development has been studied mainly using morphological techniques and especially histofluorescence. However, the biochemical characteristics of dopamine (DA) neuron development and its physiological role during ontogeny are much less known. In the present article, the biochemical development of DA neurons, from day 13 of prenatal life to adulthood, is evaluated in Sprague-Dawley rats. DA was first detected on day 14 of gestation. The brain increase in this neurotransmitter begins on day 17 in the proencephalon and on day 18 in the mesencephalon, reaching on day 20 a level similar to that found during adulthood in the latter but not in the former. DA levels in the proencephalon rise slowly to adulthood level when compared to DA in the mesencephalon. The modifications observed in tyrosine levels are also largely similar to those reported for DA. Finally, the study of the first 48 h of life shows an increase in tyrosine levels and a decrease in dihydroxyphenylacetic acid levels (with a reduction of DA turnover) during the first 4-5 h of postnatal life. Since the serotonergic modification was completely different from DA modification, we conclude that the biochemical alteration of DA neurons during early postnatal development is specific. The present data suggest that DA neurons play different roles before and after reaching adult development.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

African horse sickness in Spain.

The aetiology, pathogenesis and epizootiology of African horse sickness (AHS) are reviewed with special reference to recent outbreaks in the Iberian peninsula. AHS is a highly fatal insect-borne viral disease of Equidae. It is caused by an Orbivirus (family Reoviridae) and nine serotypes are recognised. Outbreaks occurred in central Spain in 1987 and in southern regions of the Iberian peninsula in 1988, 1989 and 1990. All were associated with serotype 4 of the virus, whereas other occurrences of AHS outside Africa have all been caused by serotype 9. The clinical picture in the outbreaks was mainly of the acute (pulmonary) form except in 1988 when the subacute (cardiac) form of disease predominated. Several hundred horses died or were destroyed as a result of the outbreaks. Further spread was contained by a combination of slaughter of sick animals, movement controls, and vaccination which was extended over an increasingly wide area in successive years. The 1987 outbreak is believed to be associated with infected zebras imported from Africa. Possible explanations for the recurrence of disease in Spain in successive years are considered to include (a) the climatic conditions in Southern Spain, which could permit continuous vector activity, (b) the relative clinical resistance of mules and donkeys, which may permit subclinical circulation of the virus, (c) incomplete population immunity among horses due to possible gaps in the vaccination strategy.

African Horse Sickness↗
PubMed1992

Coexpression of class I major histocompatibility antigen and viral RNA in central nervous system of mice infected with Theiler's virus: a model for multiple sclerosis.

Chronic infection of susceptible strains of mice with Theiler's murine encephalomyelitis virus (TMEV) results in central nervous system (CNS) demyelination similar to multiple sclerosis. Demyelination induced by TMEV is mediated, in part, by class I-restricted CD8+ T lymphocytes. For these T cells to function, they must recognize virus-infected CNS targets in the presence of class I major histocompatibility complex (MHC) antigen. Therefore, we studied in vivo expression of class I MHC antigen and viral antigen-RNA in prototypic mouse strains that are susceptible (SJL/J) or resistant (C57BL/10SNJ) to TMEV-induced demyelination. In brains of resistant mice, viral antigen-RNA expression peaked on day 3 after infection and was effectively diminished by day 5 such that few virus-infected cells were ever detected in the spinal cord. In contrast, susceptible mice demonstrated delay in clearance of TMEV from the brain and a subsequent increase and persistence of viral antigen-RNA in the spinal cord for as long as 277 days. Viral infection resulted in "upregulation" of class I MHC expression in the CNS. Class I MHC antigens were expressed as early as 1 day after infection in the choroid plexus of both strains of mice before detection of viral antigen or inflammation. In resistant mice, class I MHC expression predominated in the gray matter of the brain and spinal cord on day 7 after infection but returned to undetectable levels by day 28. In susceptible mice, class I MHC expression in the CNS persisted and was intense in the white matter of the spinal cord throughout chronic infection and demyelination. No class I MHC expression was detected in the CNS of uninfected mice. Coexpression of viral RNA and class I MHC antigen was demonstrated in CNS cells by using simultaneous in situ hybridization and immunoperoxidase technique. These results support the hypothesis that a class I-restricted immune response directed against virus-infected cells may be important in the mechanism of demyelination.

Animals↗
PubMed1992

Laterality, alternation, and perseveration relationships on the T-maze test.

The T-maze test has been used to study several entirely different issues: spontaneous alternation behavior (SAB), perseveration behavior (PB), and behavioral lateralization. Despite the fact that in this test the behavior studied is always the same one (i.e., side choice), the possible relationships among SAB, PB, and lateralization have not been previously evaluated. The present study investigated the relationships among these functions. The results demonstrated that (a) shock increases PB and lateralization but decreases SAB, (b) practice increases lateralization and decreases SAB but does not modify PB, and (c) there are sex differences for alternation and SAB. Because these functions are expressed by the same behavioral pattern, they must be quantified simultaneously to avoid mistaken conclusions when the T-maze test is used.

Animals↗
PubMed1992

NOVP and radiotherapy for early-staged Hodgkin's disease: an interim analysis.

Modern treatment plans for early staged Hodgkin's disease must focus on optimal disease-free survival results without laparotomy, minimal acute toxicity, and reduced long-term complications. We have treated 69 adult patients with stage I-II Hodgkin's disease, 40 of whom had bulky disease, B symptoms, or hilar disease, and 22 with stage III disease with 3 cycles of NOVP (Novantrone, vincristine, vinblastine, prednisone) and radiotherapy. Only patients with stage III1 disease involving the celiac axis without para-aortic or pelvic involvement, had to undergo laparotomy prior to treatment. Three patients did not respond to NOVP: two of these did not respond to MOPP or ABDIC, and two are currently without relapse following bone marrow transplant. With a median follow-up of 18 months, 62 with stage I-II and 19 with stage III remain without relapse, and 91 patients are alive. Tolerance to therapy was excellent with minimal nausea, myalgias, and alopecia. We conclude that this regimen for Hodgkin's disease provides good results for clinically staged I-III disease, but longer follow-up may demonstrate prognostic factors which will influence our results.

Antineoplastic Combined Chemotherapy Protocols↗