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Biomedical subjects

D Munoz

Publications and source records attributed to D Munoz.

At least 19 recordsLinked to original sources
PubMed2000

Accurate prediction of large antiferromagnetic interactions in high- T(c) HgBa2Ca(n-1)Cu(n)O(2n+2+delta) ( n = 2,3) superconductor parent compounds

The in-plane nearest-neighbor Heisenberg magnetic coupling constant, J, of La2CuO4, Nd2CuO4, Sr2CuO2Cl2, YBa2Cu3O6, and undoped HgBa(2)Ca(n-1)Cu(n)O(2n+2+delta) ( n = 1,2,3) is calculated from accurate ab initio configuration interaction calculations. For the first four compounds, the theoretical J values are in quantitative agreement with experiment. For the Hg-based compounds the predicted values are -135 meV ( n = 1) and approximately -160 meV ( n = 2,3), the latter being much larger than in previous cases and, for n = 3, increasing with pressure. Nevertheless, the physics governing J in all these layered cuprates appears to be the same. Moreover, calculations suggest a possible relationship between J and T(c).

Journal Article↗
PubMed2000

Tubulin immunoreactive neuronal intranuclear inclusions in the human brain.

Intranuclear filamentous and crystalline inclusion bodies have been described in the nuclei of a variety of cells in both normal and pathological states. The functional significance of these structures remains to be elucidated. Moreover, although the proteinaceous nature of these inclusions has been inferred in some histochemical studies, the identity of their constituent proteins remains to be determined. In the present study, immunohistochemistry was used to investigate the presence of intranuclear inclusions in neurones of the human brain which are intensely immunoreactive for the neuronal cytoskeletal protein class III beta tubulin. The ability to label these structures immunohistochemically was exploited to investigate the topographic pattern of distribution of these inclusions in the human brain. Intranuclear inclusions were rod-shaped, polygonal, or irregular in shape. They were present in neurones and ependymal cells. Intranuclear inclusion-bearing neurones were distributed in an anatomically heterogeneous pattern in the brain. Areas exhibiting relatively high densities of inclusions included the substantia inominata and anterior olfactory nucleus, dentate gyrus, substantia nigra, inferior olivary nucleus, and dentate nucleus of the cerebellum. In addition, intranuclear inclusions were prevalent in neurones in layers II, V, and VI of the cerebral cortex. They were particularly prevalent in the mesial basal temporal neocortex. The relationship of these structures to the intranuclear rods and sheets of the classical microscopists is uncertain. The demonstration that they are composed, at least in part, of tubulin, a major cytoskeletal protein, provides important clues regarding the mechanisms underlying their formation and provides a springboard for developing hypotheses regarding their functional significance. Furthermore, the ability to demonstrate these inclusions immunohistochemically provides an avenue for further studies directed at elucidating the potential involvement of these inclusions in various pathological settings.

Adult↗
PubMed1999

Correlation between MRI and clinico-pathological manifestations in Lewis rats protected from experimental allergic encephalomyelitis by acylated synthetic peptide of myelin basic protein.

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease of the central nervous system which constitutes an accepted animal model for multiple sclerosis (MS). The disease can take an acute or chronic form depending on the injection route, animal strain and nature of the disease-inducing antigen administered. The neuroinflammation associated with the acute form can be detected with T2-weighted, T1-weighted and diffusion MRI, and blood-brain barrier changes can be investigated with Gd-DTPA-enhanced T1-weighted imaging, similar to that of MS patients. A synthetic peptide of myelin basic protein (MBP) encephalitogenic for the Lewis rat (MBP 68-86) was acylated by the attachment of a palmitoyl residue (PAL68-86), and was shown to confer almost complete protection against EAE, when administered to rats before and after an encephalitogenic challenge. In this study, treatment of Lewis rats with PAL68-86 prevented the appearance of clinical signs (p < 0.0001) after challenge with the native peptide (p68-86) in complete Freund's adjuvant (CFA), and reduced considerably the MRI and histopathological signs of the disease (p < 0.0001). Measurement of the gadolinium leakage due to neuroinflammation revealed a significant decrease in permeability from 4.09 +/- 2.1 to 2.95 +/- 1.79% pixels > mean + 2 SD (p = 0.011). Therefore, quantitative MRI measurements correlate very well with the reduced cellular infiltration in the CNS and the absence of clinical signs in the EAE-protected animal.

Acylation↗
PubMed1999

Chromogranin A in the central nervous system of the rat: pan-neuronal expression of its mRNA and selective expression of the protein.

Chromogranin A, a glycoprotein stored in secretory granules of neuroendocrine cells, displays a widespread distribution throughout the central nervous system of a variety of species. In situ hybridization histochemistry was employed to investigate the localization of chromogranin A mRNA in the central nervous system of the rat. The previously characterized monoclonal antibody, LK2H-10, was employed in an immunohistochemical study to compare the topographic localization of the chromogranin A protein with that of its mRNA. Although the latter, as revealed by in situ hybridization, displayed a ubiquitous, pan-neuronal localization throughout the rat brain, LK2H-10 immunoreactive cell bodies and axon terminals were disposed in a widespread, but highly regionally differential, distribution. This discrepancy suggests that chromogranin A is processed in a regionally differential fashion in the rat brain to yield one or multiple variant forms, one of which is specifically recognized by LK2H-10. Catecholaminergic cell groups consistently displayed LK2H-10 immunoreactivity. LK2H-10 immunopositive axon terminals were prominent in the circumventricular organs. In addition, LK2H-10 immunoreactivity was also detected in a subset of astrocytes which demonstrated a widespread, but anatomically restricted, pattern of distribution. Consequently, the variant of chromogranin A labelled by LK2H-10 represents a novel neurochemical marker for regionally differential astrocytic diversity.

Animals↗
PubMed1998

Naturally occurring deletion mutants are parasitic genotypes in a wild-type nucleopolyhedrovirus population of spodoptera exigua

A wild-type nucleopolyhedrovirus (NPV) isolate from Spodoptera exigua from Florida (Se-US2) is a variant of the SeMNPV type strain since it has a unique DNA profile but is closely related to other known geographical isolates of SeMNPV. It consists of several genotypic variants, of which seven were identified in a Se-US2 virus stock by a modification of the in vivo cloning method developed by Smith and Crook (Virology 166:240-244, 1988). The US2A variant was the most prevalent genotype, and it was designated the prototype Se-US2 variant, while four of the variants (US2B, US2D, US2F, and US2H) were found at low frequency. US2C and US2E were also very abundant, and their diagnostic bands were easily observed in wild-type isolate restriction endonuclease patterns. The analysis of each variant, compared to the prototype US2A, showed that US2B and US2H presented minor differences, while US2D and US2F contained slightly larger insertions or deletions. Variants US2C and US2E contained major deletions of 21.1 and 14 kb, respectively, mapping at the same genomic region (between 14.5 and 30.2 map units [m.u.] and between 12.8 and 23 m.u., respectively). This is the first report of such deletion mutants in a natural baculovirus population. Variants US2A, US2B, US2D, US2F, and US2H were isolated as pure genotypes, but we failed to clone US2C and US2E in vivo. When these two variants appeared without apparent contamination with any other variant, they lost their pathogenicity for Spodoptera exigua larvae. A further biological characterization showed evidence that these two naturally occurring deletion mutants act as parasitic genotypes in the virus population. Bioassay data also demonstrated that pure US2A is significantly more pathogenic against second-instar S. exigua larvae than the wild-type isolate. The need for precise genotypic characterization of a baculovirus prior to its development as a bioinsecticide is discussed.

Journal Article↗
PubMed1997

Anisakis simplex, a relevant etiologic factor in acute urticaria.

Anisakis simplex, a parasite of fish and cephalopods, can induce IgE-mediated reactions. This study aimed to determine the etiologic role of A. simplex in patients affected by urticaria/angioedema (AE) or anaphylaxis. We studied 100 adult subjects suffering acute episodes of urticaria/AE, by anamnesis, prick tests with A. simplex and fish-mix extracts, and total and specific IgE to both A. simplex and cod. The following criteria of A. simplex allergy were considered: 1) urticaria/AE within 6 h after fish ingestion; 2) specific IgE to A. simplex; 3) positive prick test to A. simplex extract; 4) exclusion of other suspected causes. Double-blind, placebo-controlled food challenge was not carried out because ethical considerations forbid challenge with a parasite. Specific IgE to A. simplex (> 0.7 kU/l) was found in 22 subjects, but only eight were diagnosed as having A. simplex allergy. Other allergens were involved in 37 patients, and 55 cases were considered idiopathic. Specific IgE to fish (> 0.7 kU/l) was found in two patients, but only one was diagnosed as having fish allergy. We concluded that A. simplex is an important etiologic factor in acute urticaria. We suggest that it should be considered in cases of urticaria/AE or anaphylaxis, especially after fish ingestion.

Adolescent↗
PubMed1996

Clinical and pathological characteristics of primary progressive aphasia and frontal dementia.

The recently described conditions of primary progressive aphasia and frontal lobe dementia overlap clinically and pathologically to a considerable extent with each other and with clinical and pathological descriptions of Pick's disease. Our clinical and neuropathological experience is summarized, leading us to the conclusion that the degree of overlap justifies the concept of "Pick complex" to include, in addition to the above, corticobasal ganglionic degeneration and some instances motor neuron disease with dementia.

Aphasia, Primary Progressive↗
PubMed1996

Malignant rhabdoid tumor of brain: an aggressive clinical entity.

OBJECTIVE: We report three patients with malignant rhabdoid tumor (MRT) of the brain, two children and an adult. There were three purposes to this report: to describe the clinical course in an adult with MRT; to describe the interesting histopathological metamorphosis of one of the tumors; and to report the outcome of the treatment regimens we used in order to help guide future treatment. Since these tumors are quite rare it is important to continue to try new regimens in the search for effective therapy rather than to repeat ineffective ones. METHOD: Report of three patients. RESULTS: The clinical course in all three patients was typical of these aggressive neoplasms in that chemotherapy and radiotherapy were ineffective in modifying the rapid deterioration leading to death. CONCLUSIONS: MRT can occur in adults. Autopsy in one patient showed that the tumor seemed to undergo an evolution in appearance when compared with the original pathology specimen from craniotomy. Administration of systemic therapy should be prompt and include intrathecal chemotherapy.

Adult↗
PubMed1996

Spodoptera exigua multicapsid nucleopolyhedrovirus deletion mutants generated in cell culture lack virulence in vivo.

The baculovirus Spodoptera exigua multicapsid nucleopolyhedrovirus (SeMNPV) has high potential for development as a bio-insecticide for control of the beet armyworm (S. exigua). It is highly infectious for S. exigua larvae and its host range is very narrow. A prerequisite for such application is the possibility of growing this virus in large quantities, e.g. in insect cell lines. It was observed, however, that polyhedra of SeMNPV plaque-purified in Se-UCR1 cells did not cause larval mortality or morbidity when fed to S. exigua larvae. As this suggested a genetic alteration in in vitro produced SeMNPV, comparative restriction analysis of in vitro and in vivo produced SeMNPV DNA was performed. The restriction patterns of viral DNA from several different plaques always differed from that of the wild-type in the same way, suggesting that a large, single deletion had occurred in the in vitro produced viral genome. In order to localize this deletion more precisely a detailed physical map of the wild-type SeMNPV genome was constructed, using the restriction endonucleases XbaI, BamHI, Bg/II, PstI, SstI, HindIII and SpeI. In addition, the entire SeMNPV genome was cloned into a library containing five overlapping cosmids and a plasmid library. About 80 restriction sites were located and the orientation of the map was set according to the location of the polyhedrin and p10 genes. The approximate size of the viral genome was 134 kbp. Based on this map it could be established that mutant SeMNPV, obtained by passage in cell culture, contained a single deletion of approximately 25 kbp between map units 12.9 and 32.3.

Animals↗
PubMed1994

Neuropathology of intracranial arteriovenous malformations following conventional radiation therapy.

Conventional fractionated radiation therapy was used in 15 patients to treat arteriovenous malformations (AVMs) of the brain deemed inoperable or incompletely obliterated using endovascular or surgical techniques. The AVMs measured from 0.8 to 85 cm3 (mean 28.2 cm3; median 24 cm3). Angiography in 12 patients 1-21 years following radiation therapy demonstrated no significant change in 7, slight reduction in 2, near complete obliteration in 1, and complete obliteration in 2. Magnetic resonance imaging further demonstrated apparent obliteration in one other case. Three irradiated AVMs were available for pathological examination following fatal recurrent hemorrhage after 21 years in case 1 and following surgery after 5 years in cases 2 and 3. Doses of 20 and 45 Gy were delivered to the area of the AVM in 10 and 15 fractions with a 6-MV linear accelerator in case 1 and in cases 2 and 3, respectively. A blinded histopathological comparison was made of the latter cases and three AVMs removed at surgery that were not previously irradiated and that were comparable in size, number of arterial feeders, and location within the brain. Segmental hyalinization of some blood vessels was seen in both irradiated and nonirradiated cases. The single postmortem specimen showed extensive thrombosis but a patent nidus. The findings are in keeping with the clinical impression that conventional fractionated radiation therapy fails to alter the natural history of cerebral AVMs. The favorable outcome of radiosurgery on small- to medium-sized AVMs appears attributable to the shorter duration of therapy using relatively high-dose prescriptions to the nidus.

Adult↗
PubMed1992

Formation of ion-permeable channels by tumor necrosis factor-alpha.

Tumor necrosis factor-alpha (TNF, cachectin), a protein secreted by activated macrophages, participates in inflammatory responses and in infectious and neoplastic disease states. The mechanisms by which TNF exerts cytotoxic, hormonal, and other specific effects are obscure. Structural studies of the TNF trimer have revealed a central pore-like region. Although several amino acid side chains appear to preclude an open channel, the ability of TNF to insert into lipid vesicles raised the possibility that opening might occur in a bilayer milieu. Acidification of TNF promoted conformational changes concordant with increased surface hydrophobicity and membrane insertion. Furthermore, TNF formed pH-dependent, voltage-dependent, ion-permeable channels in planar lipid bilayer membranes and increased the sodium permeability of human U937 histiocytic lymphoma cells. Thus, some of the physiological effects of TNF may be elicited through its intrinsic ion channel-forming activity.

Cell Membrane Permeability↗
PubMed1984

In vivo effects of nipecotic acid on levels of extracellular GABA and taurine, and hippocampal excitability.

The effect of nipecotic acid on the extracellular levels of the putative hippocampal inhibitory transmitters, gamma-aminobutyric acid (GABA) and taurine, and also excitability in the dentate gyrus, were studied in anaesthetised rats using the dialytrode technique. The dentate gyrus was perfused by means of a dialytrode , using Krebs-Ringer bicarbonate or nipecotic acid solutions. Dentate field potentials, evoked by electrical stimulation of the perforant pathway, were recorded. Nipecotic acid drastically elevated the levels of extracellular GABA and taurine and the amplitude of population spikes in the dentate was concomitantly decreased. These results indicate that changes in extracellular levels of endogenous GABA and/or taurine influence the excitability of the hippocampus.

Animals↗