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Biomedical subjects

M Rodriguez

Publications and source records attributed to M Rodriguez.

At least 37 records · Page 2Linked to original sources

Factors associated with detection of human papillomavirus E4 and L1 proteins in condylomata acuminata.

The E4 and L1 gene products of human papillomavirus (HPV) types 6 and 11 are detected in variable amounts in condylomata acuminata. To study factors associated with detection of these proteins, biopsy specimens containing HPV-6 or -11 were analyzed for E4 protein, L1 protein, and HPV copy number. Seventeen of 50 women biopsied were pregnant. Nine men were also biopsied. Both the E4 and L1 proteins were found more frequently in lesions from pregnant women than from nonpregnant women or men. Both proteins were more often detected in lesions from women than from men. E4 gene products were more often detected in lesions in which L1 protein was detected and a higher HPV copy number was present. Detection of E4 gene products correlates with the detection of L1 protein in condylomata acuminata caused by HPV-6 or -11.

Adult

Differences in the motor response to apomorphine between untreated and fluctuating patients with Parkinson's disease.

Behavioral hyposensitivity to repeated apomorphine administration has been observed in fluctuating parkinsonian patients. To investigate whether a similar phenomenon occurs in patients never treated with levodopa, we studied the response to apomorphine in 20 de novo patients with Parkinson's disease. Six patients showed no or minimal improvement after apomorphine injections (maximal dose 3.5 mg). Fourteen patients responded and were then given up to four repeated subcutaneous injections of apomorphine [minimal effective dose (MED)]. The responses of de novo patients were compared with responses in 10 patients with motor fluctuations previously studied by the same protocol. There was no significant difference in latency and duration of motor responses after repeated apomorphine injections in de novo patients. MED was similar in de novo and fluctuating patients, but duration of improvement induced by each apomorphine bolus was longer in the de novo group. These results indicate that response duration to apomorphine is longer in previously untreated patients and that behavioral tolerance associated with pulsatile dopaminergic stimulation by apomorphine occurs mainly in patients with more advanced disease under chronic levodopa therapy.

Adult

Pathogenesis of early and late disease in mice infected with Theiler's virus, using intratypic recombinant GDVII/DA viruses.

Intratypic recombinant Theiler's viruses prepared between GDVII and DA strains were used to identify genomic sequences important in neurovirulence, virus persistence, and demyelination and to clarify the mechanisms involved in disease induction. The coding region between 1B and 2C of the highly virulent GDVII strain contains a determinant partly responsible for neurovirulence (early paralysis and death) which correlates with elevated levels of infectious virus and the presence of virus antigen within neurons of the brain stem and gray matter of the spinal cord. Both the GDVII and the DA strains of virus contain genetic determinants for late demyelination in spinal cord. However, quantitative analysis of demyelination produced by recombinant GDVII/DA viruses suggest that multiple gene segments influence the number and extent of demyelinating lesions.

Animals

Silent and expressed sister Mup genes are located within distinct chromatin domains: analysis by pulsed-field gel electrophoresis and polymerase chain reaction-supplemented DNase I digestion.

We have recently described a subfamily of two genes, Mup-1.5a and Mup-1.5b, which exist as a nonallelic pair in most inbred strains of mice. The Mup-1.5a and Mup-1.5b genes are more than 99.9% homologous, yet they are differentially expressed. While the Mup-1.5a gene is expressed at a high level in the submaxillary gland, the Mup-1.5b gene does not appear to be expressed either in this or in any other tissue. The Mup-1.5b gene can, however, be expressed as a transgene with the tissue specificity of its sister gene, Mup-1.5a. We have shown before that both the Mup-1.5a and Mup-1.5b genes are located on chromosome 4, closely linked to the Mup-1 locus. In this report, we demonstrate the two genes are located within distinct chromosomal domains, separated by at least 150 to 200 kb of DNA. Using a novel method, detailed in this report, we show that in the submaxillary gland, the Mup-1.5a gene is five- to sixfold more susceptible to DNase I digestion than is the Mup-1.5b gene. This finding suggests that the inactivity of the Mup-1.5b gene is brought about by long range-acting mechanisms that establish a chromatin structure in the vicinity of this gene incompatible with transcription.

Animals

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