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Biomedical subjects

M Rodriguez

Publications and source records attributed to M Rodriguez.

At least 469 records · Page 26Linked to original sources

Abnormal muscle and skin mitochondria in family with myoclonus, ataxia, and deafness (May and White syndrome).

A mother and two of her daughters had deafness and cortical reflex myoclonus; the mother also had mild truncal ataxia. Muscle and skin biopsy specimens revealed abundant ragged-red fibres and abnormal mitochondria. The son of one of the daughters had sensorineural deafness. Three other grandchildren were asymptomatic. The two daughters also had diabetes mellitus, hypertension and cardiomyopathy. Another daughter died of renal failure. The mother lost her hearing in her 70s, one daughter in her 30s, and the other daughter and the grandson in their 20s. The mother has had transient episodes (24-48 hours) of temporal disorientation, severe action myoclonus, and ataxia for about eight years. This is the first reported family with inherited deafness, myoclonus, and ataxia with mitochondrial pathology.

Adolescent↗

Effect of restricted feeding, fasting, and diabetes on the relationship between thyroid hormone receptor occupancy, growth hormone induction, and inhibition of thyrotropin release in thyroidectomized rats.

The present study was undertaken to test the effect of food restriction, fasting, and diabetes on the relationship between thyroid hormone receptor occupancy and two biological end points, GH production and the inhibition of TSH secretion, in thyroidectomized rats. The estimated maximal binding capacity (MBC) in diabetic (D) and fasting (F) rats and in animals limited to 25% (FR25) of the food consumption of normal (C) rats was decreased to 57%, 73%, and 76%, respectively, of C values (P < 0.01-0.001), whereas normal values were found in thyroidectomized (Tx) rats and in animals limited to 50% (FR50) of the food intake of C animals. The nuclear T3 content and T3 receptor occupancy were reduced, respectively, to 25% and 29% in Tx, 77% and 81% in FR50, 52% and 69% in FR25, 49% and 66% in F, and 36% and 64% in D rats of the corresponding C values (P < 0.05-0.001). Pituitaries from Tx, FR50, FR25, F, and D rats contained less GH than C pituitaries (0.14%, 81%, 69%, 88%, and 51%, respectively, of C pituitaries; P < 0.05-0.001). Plasma TSH was lower in FR50, FR25, F, and D rats than in C animals (78%, 57%, 52%, and 48%, respectively (P < 0.01-0.001)), and markedly increased in Tx animals. Administration of a single dose of 2, 5, or 10 micrograms T3/100 g BW to Tx C, Tx FR50, TX FR25, Tx F, and Tx D rats resulted in a similar and progressive increase in nuclear T3 in all groups, except for lower values in Tx D animals. However, receptor occupancy did not differ among the different groups at each T3 dose. This treatment resulted in a progressive increase in pituitary GH in all groups; however, in Tx FR50, Tx FR25, Tx F, and Tx D pituitaries, the GH responses to 10 micrograms T3 were only 77%, 59%, 44%, and 27%, respectively, of that in Tx C rats. (P < 0.05-0.001). Moreover, significant differences in the GH response to 10 micrograms T3 were observed among Tx FR50, Tx FR25, Tx F, and Tx D animals (P < 0.01-0.001). In addition plasma TSH levels in untreated Tx FR50, Tx FR25, Tx F, and Tx D rats were only 88%, 82%, 79%, and 72%, respectively, of that in Tx C animals (P < 0.05-0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Immunosuppression promotes CNS remyelination in chronic virus-induced demyelinating disease.

Immunosuppression using cyclophosphamide or anti-T cell monoclonal antibodies (mAbs) directed at CD4 or CD8 promoted remyelination of CNS axons in the spinal cords of mice infected chronically with Theiler's virus. Treatment with a mAb directed at class II major histocompatibility gene products did not increase the extent of CNS remyelination. Following immunosuppressive treatment, quantitative morphometry revealed a five- to sevenfold increase in new myelin synthesis. Proliferating nervous system cells were identified at the edges of remyelinated lesions by their incorporation of [3H]thymidine. CNS remyelination occurred in mice depleted of selected subsets of T lymphocytes despite the local persistence of viral antigen. These findings indicate that CNS remyelination occurs as a normal consequence of primary myelin injury, but factors associated with immune T cells somehow impair remyelination. Interference with the function of immune T cells enhances CNS remyelination by oligodendrocytes. Similar depletion of immune T cells may allow for enhanced remyelination in the CNS of patients with chronic multiple sclerosis.

Animals↗

Time interval between repeated injections conditions the duration of motor improvement to apomorphine in Parkinson's disease.

Behavioral hyposensitivity to repeated apomorphine administration occurs in fluctuating parkinsonian patients. To determine to what extent the interval between doses influences the response, we administered equal paired apomorphine injections to 10 fluctuating parkinsonian patients. Subjects received two apomorphine injections at 2-hour and at 4-hour intervals on different days after a 10- to 12-hour overnight period without levodopa. Following apomorphine doses at 2-hour intervals, the duration of response was reduced by 40% (61 versus 42 minutes, p less than 0.001) but was of equal duration when the doses were given at 4-hour intervals. These findings indicate that the interval between doses is a critical determinant of motor response. We postulate a time-dependent period of partial hyposensitivity to pulsatile DA stimulation.

Adult↗

Visual evoked potentials, attention and mnemonic abilities in children.

We analyzed the correlation between attention and mnemonic processes and different visual evoked potential (VEP) parameters. A group of 34 children between 9 and 13 years old was studied. VEPs were recorded in C3, C4, P3, P4, O1, O2, T5 and T6 with linked ear lobes as reference. Two different types of stimuli were used: flash and checkerboard pattern. The power of VEPs was calculated as the sum of the square amplitude values for different time epochs. Correlation coefficients between left and right homologous VEPs were also computed. A visual selective attention task divided into 5 items of increasing difficulty and the Sternberg paradigm were applied. The performance was automatically evaluated by the computer, giving the number of correct responses (NCR) and other measures of performance. Correlation coefficients between VEP parameters and the scores obtained in the performance of tasks were calculated. It was observed that power in P3, P4, T5, and T6 and the correlation coefficients between central, parietal and temporal VEPs were positively correlated with NCR of both tasks. However, power in O1 and O2 was negatively correlated with NCR.

Adolescent↗

Characterization of the nuclear receptors of triiodothyronine (T3) by immunocytochemistry under electron microscopy.

By immunocytochemical methods, using colloidal gold particles coupled to antibodies, it is possible to label the occupied nuclear T3 receptors and observe them by electron microscopy. We carried out some experiments to validate these methods by testing the absence of non-specific binding of the antibodies to subcellular structures different from the T3 receptors. So, we have verified that the number of occupied T3 receptors in tissues from normal rats is lower in kidney cells than in heart and liver ones, a finding which is an agreement with data reported by others. The occupation of the receptors increases after T3 administration and decreases by triiodothyroacetic acid (Triac) administration to the rats, due to the displacement of T3 from the receptors with the latter. Our results are similar to those of the other authors using radioactive tracers. Non-specific binding was not detected. The occupied T3 receptors labelled with colloidal gold particles are located most commonly in the hetero/euchromatin interface. From our results we conclude that the colloidal gold particles observed by electron microscopy specifically label occupied T3 receptors, and the determination of the thyroid status at cellular level can be achieved using electron microscopy after labelling the receptors by immunocytochemistry with colloidal gold particles coupled to antibodies.

Animals↗

Effects of growth hormone in patients receiving total parenteral nutrition following major gastrointestinal surgery.

The purpose of the present study was to determine whether the administration of a biosynthetic human growth hormone was capable of enhancing the efficacy of total parenteral nutrition. Patients (n = 38) who had undergone major gastrointestinal surgery were randomly divided into two groups. Group I (n = 20) treated only with PN, and Group II (n = 18) treated as in Group I plus human growth hormone (4 IU daily). Our study shows that the administration of human growth hormone produces a statistically significant increase in serum levels of growth hormone, somatomedin-C, transferrin, albumin and total proteins. It also causes a positive nitrogen balance from the first 24 hours onward. These findings suggest that the administration of human growth hormone produces an increase in protein synthesis, perhaps through somatomedin-C as mediator.

Adult↗

Reduced peptide bond pseudopeptide analogues of neurotensin: binding and biological activities, and in vitro metabolic stability.

A series of pseudopeptide analogues of neurotensin was produced by systematically replacing the five peptide bonds in neurotensin-(8-13) with CH2NH (psi, reduced) bonds. All these analogues were synthesized with a free amino terminus (H derivatives) and with a N-terminal tert-butyloxycarbonyl group (Boc derivatives). The compounds were screened in vitro for agonist or antagonist activity and for metabolic stability by testing (1) their ability to inhibit the binding of radiolabelled neurotensin to homogenates of newborn mouse brain; (2) their ability to contract isolated guinea-pig ileum preparations; and (3) their degradation in the presence of rat brain homogenates. All the analogues bound to the mouse brain neurotensin receptor and all exhibited agonist activity in the guinea-pig ileum assay. Only the H- and Boc-[psi 8,9] derivatives were at least as potent as their parent compounds neurotensin-(8-13) and Boc-neurotensin-(8-13) in the binding and biological assays. All the other pseudopeptide analogues with reduced bonds at position 9-10, 10-11, 11-12 and 12-13 showed a marked reduction in potency ranging from 2 to 4 orders of magnitude. All the derivatives that were protected at their N terminus either by the presence of a Boc group or by the presence of a reduced bond at position 8-9 and 9-10 were slowly degraded by rat brain homogenates. The other derivatives were, in contrast, quite rapidly degraded. There was a good correlation between binding and biological potencies for those analogues that were resistant to degradation. Interestingly, the degradation-resistant H-[psi 8,9] compound exhibited higher binding and biological potency then neurotensin. It is therefore expected that this analogue will produce highly potent and long-lasting neurotensin-like effects in vivo, and preliminary experiments indicate that this is indeed the case.

Amino Acid Sequence↗

Expression of human HLA-B27 transgene alters susceptibility to murine Theiler's virus-induced demyelination.

Infection of certain strains of mice with Theiler's murine encephalomyelitis virus results in persistence of virus and an immune-mediated primary demyelination in the central nervous system that resembles multiple sclerosis. Because susceptibility/resistance to demyelination in B10 congeneic mice maps strongly to class I MHC genes (D region) we tested whether expression of a human class I MHC gene (HLA-B27) would alter susceptibility to Theiler's murine encephalomyelitis virus-induced demyelination. Transgenic HLA-B27 mice were found to co-express human and endogenous mouse class I MHC genes by flow microfluorimetry analysis of PBL. In the absence of the human transgene, H-2stf, or v mice but not H-2b mice had chronic demyelination and persistence of virus at 45 days after infection. No difference in degree of demyelination, meningeal inflammation, or virus persistence was seen between transgenic HLA-B27 and nontransgenic littermate mice of H-2f or H-2v haplotype. In contrast, H-2s (HLA-B27+) mice showed a dramatic decrease in extent of demyelination and number of virus-Ag+ cells in the spinal cord compared with H-2s (HLA-B27-) littermate mice. In addition, none of the eight H-2s mice homozygous for HLA-B27 gene had spinal cord lesions even though infectious virus was isolated chronically from their central nervous system. Expression of HLA-B27 transgene did not interfere with the resistance to demyelination normally observed in B10 (H-2b) mice. These experiments demonstrate that expression of a human class I MHC gene can modulate a virus-induced demyelinating disease process in the mouse.

Animals↗

Trafficking of lipids from the endoplasmic reticulum to the Golgi apparatus in a cell-free system from rat liver.

Trafficking and sorting of lipids during transport from the endoplasmic reticulum to the Golgi apparatus was studied using a cell-free system from rat liver. Transitional elements of the endoplasmic reticulum were prepared from liver slices prelabeled with [14C]- or [3H]acetate as the donor fraction. Non-radioactive Golgi apparatus were immobilized on nitrocellulose as the acceptor. When reconstituted, the radiolabeled donor retained a capacity to transfer labeled lipids to the non-radioactive Golgi apparatus acceptor. Transfer exhibited two kinetically different components. One was stimulated by ATP, facilitated by cytosol and inhibited by guanosine 5'-O-(thiotriphosphate) and N-ethylmaleimide. In parallel with protein transport, the ATP-dependent lipid transfer occurred with a temperature transition at about 20 degrees C. The other was not stimulated by ATP, did not require cytosol, was acceptor unspecific, was unaffected by inhibitors and, while temperature dependent, did not exhibit a sharp temperature transition. The ATP-independent transfer was non-vesicular. In contrast, the ATP-dependent transfer was vesicular. Transition vesicles isolated by preparative free-flow electrophoresis, when used as the donor fraction, transferred lipids to Golgi apparatus acceptor with a 5-6-fold greater efficiency than that exhibited by the unfractionated transitional endoplasmic reticulum. Formation of transition vesicles was ATP-dependent. Transferred lipids were chiefly phosphatidylcholine and cholesterol. Membrane triglycerides, major constituents of the transitional endoplasmic reticulum membranes, were both depleted in the transition vesicle-enriched fractions and not transferred to Golgi apparatus suggestive of lipid sorting prior to or during transition vesicle formation. The characteristics of the ATP plus cytosol-dependent transfer were similar to those for protein transfer mediated by transition vesicles. Thus, the 50-70-nm vesicles derived from transitional endoplasmic reticulum appear to function in the trafficking of both newly synthesized proteins and lipids from the endoplasmic reticulum to the Golgi apparatus.

Adenosine Triphosphate↗

Behavioral lateralization in rats: prenatal stress effects on sex differences.

The possible relationship between human and animal asymmetries is currently a controversial point. In the present study we report that, after practice, rat behavioral asymmetry presents important similarities with human laterality. Thus, rat behavior presents: (1) absolute and population laterality to the same degree and with the same right-bias as that reported for humans; (2) the female has less absolute laterality but similar population laterality to the male; (3) male-female differences for behavioral laterality are modified by prenatal stress as occurs with similar other hormone-regulated behavior.

Analysis of Variance↗

The treatable dementia of Sjögren's syndrome.

Progressive dementia developed during a 15-month period in a 56-year-old woman with serologically and clinically documented primary Sjögren's syndrome. Findings from magnetic resonance imaging and angiography were normal, but a brain biopsy disclosed perivascular lymphocytic inflammation in leptomeningeal and parenchymal vessels. Treatment with high-dose corticosteroids produced rapid and nearly complete resolution of the dementia.

Alzheimer Disease↗

Detection of human papillomavirus types 6 and 11 E4 gene products in condylomata acuminatum.

Polyclonal antiserum to an Escherichia coli-produced beta-galactosidase/E4 fusion protein of human papillomavirus type 6b (antiserum 256), and affinity purified HPV 11 anti-E4 antibodies were tested for reactivity in Western blots with bacterially expressed trpE/E4 fusion proteins of HPV types 6b, 11, 16, and 18. To further characterize the affinity purified anti-E4 antibodies, a dot-immunobinding assay was performed using overlapping synthetic HPV 11 E1E4 peptides as antigens. Protein extracts of condylomata acuminatum from 18 patients containing HPV type 6 or 11 DNA sequences were tested in Western blots using antiserum 256 or affinity purified HPV 11 anti-E4 antibodies. In the Western blots of the trpE proteins, antiserum 256 identified the HPV types 6b and 11 fusion proteins; the affinity purified HPV 11 anti-E4 antibodies identified only the HPV 11 fusion protein. In the dot-immunobinding assay, three HPV 11 peptides were recognized, each containing a shared 8 amino acid sequence that differs significantly from the corresponding sequences of HPV types 6b, 16, or 18. In the Western blots of protein extracts from 18 condylomata acuminatum samples shown to contain HPV types 6 or 11 DNA, putative E4 gene products were identified in six samples by antiserum 256. The affinity purified HPV 11 anti-E4 antibodies identified putative E4 gene products in one of these same six lesions, which was shown to contain HPV 11 sequences by the Southern blot method. All six samples containing E4 gene products were from women. Three of these women were pregnant, one had serum antibodies to the human immunodeficiency virus, and one was a renal transplant recipient receiving glucocorticoids.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

Fetal brain serotonin synthesis and catabolism is under control by mother intake of tryptophan.

Previous morphological studies reported that serotonergic neurons appear in rats in the second half of prenatal life. Initially the biochemical differentiation of these neurons before birth was studied. Both serotonin (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) was detected in the fetal brain on day 15 of gestation. During prenatal development an increase was detected in the brain levels of 5-HT (200% higher on day 19 than on day 15) and 5-HIAA (700% higher on day 19 than on day 15). Oral administration of tryptophan to pregnant rats induced a dose-related increase of tryptophan concentration in different fetal tissues, including brain. The increase in tryptophan tissue concentration was detected for low doses (50 mg/kg) and remained unsaturated after administration of high doses (1000 mg/kg). This observation suggests that the placental barrier is not effective to block the influx of high levels of tryptophan to the fetus. Tryptophan concentration in the brain is 300% higher than in the carcass and 600% higher than in the placenta. These data suggest a mechanism to assume a role in concentrating of tryptophan in the brain. Finally, it was found that an increase in brain tryptophan induced changes in both serotonin and 5-HIAA brain levels, but did not modify tyrosine, dopamine or norepinephrine levels. Thus, under physiological conditions, tryptophan hydroxylase activity in prenatal brain is probably not saturated by its substrate tryptophan.

Animals↗

Sex differences in behavioral despair: relationships between behavioral despair and open field activity.

Many studies have reported sex differences in the rates of depression in humans. Due to experimental problems, the nature of these sexual differences is still unknown. In the present study, we quantify the sex differences in depression using two animal models. Both the Porsolt et al. test and the Hilakivi and Hilakivi forced swimming test have shown that the duration of immobility is higher in the male than in the female. Sexual differences in the animal models of depression are probably unrelated to general activity differences because there is no significant correlation between activity in both tests. However, the correlation between the two models of depression used reached statistical significance. Finally, the immobility levels in the Porsolt test were similar in the different stages of the estrous cycle.

Animals↗

Role of T cells in resistance to Theiler's virus infection.

Intracerebral infection of C57BL/10SNJ mice with Theiler's virus results in acute encephalitis with subsequent virus clearance and absence of spinal cord demyelination. In contrast, infection of SJL/J mice results in acute encephalitis, virus persistence, and immune-mediated demyelination. These experiments examined the role of T-cell subsets in the in vivo immune response to Theiler's virus in resistant C57BL/10SNJ mice. Depletion of T-cell subsets with monoclonal antibodies (mAbs) directed at CD3 (pan-T-cell marker), CD4+ (class II-restricted) or CD8+ (class I-restricted) T cells resulted in increased frequency of paralysis and death as a result of acute encephalitis. Neuropathologic studies 10 days after infection demonstrated prominent necrosis, primarily in the pyramidal layer of hippocampus and in the thalamus of mice depleted of T-cell subsets. In immunosuppressed and infected C57BL/10SNJ mice, analysis of spinal cord sections 35 days after infection demonstrated small demyelinated lesions relatively devoid of inflammatory cells even though virus antigen could be detected by immunocytochemistry. Both CD4+ and CD8+ T cells are important in the resistance to infection with Theiler's virus in C57BL/10SNJ mice. However, subsequent spinal cord demyelination, to the extent observed in susceptible mice, depends on the presence of virus antigen persistence and a competent cellular immune response.

Animals↗

Inequalities in health in intensive care patients.

In order to study the possible association between socioeconomic status (SES) and critical care mortality, we examined a cohort of 847 patients over 14 years of age, as they were consecutively admitted to three general intensive care units (ICUs). The patients with low SES (social classes IV and V according to the British Registrar General's classification) were older (62.0 v 58.5 years old, p less than 0.0001) and showed a higher ICU mortality (odds ratio (OR) = 1.61, p = 0.0204) and severity of illness on admission (mean Simplified Acute Physiology Score [SAPS] 9.9 vs 8.7, p = 0.0002) than patients with high SES (social classes I-III). The initial severity of illness differential was detected both in patients admitted from the emergency area and in patients admitted from the general hospitalization ward, suggesting the existence of some kind of preselection procedure related to the SES of the patient. The stepwise logistic regression analysis identified as independent predictive variables of ICU mortality therapeutic effort (measured with the Therapeutic Intervention Scoring System [TISS]), SAPS score, age and hospital, but not SES. The TISS/SAPS ratio according to origin of patients (emergency/general wards) was comparable in the high and low SES. We conclude that there is an inverse relationship between SES and ICU mortality. The mortality excess in the low SES patients is largely accounted for by the covariates of the low SES (especially their high age and severity of illness on admission). There is no evidence of a different relative therapeutic effort according to the SES.

Adolescent↗