Biomedical subjects

F Vega

Publications and source records attributed to F Vega.

At least 55 records · Page 3Linked to original sources

PubMed1994

[Characterization of chromosomal rearrangements by in situ hybridization in glioblastoma].

In a case of glioblastoma, the following karyotype was determined: 47, X, - Y, + der(1) t(1;9)(p21;p23), t(1;9)(p21;p23), + 3, + 7, der(9) t(Y;9)(q11;p21), - 13, t(13;16)(p13,p11), del(14)(q11q22). Classical satellite DNAs are mainly located in chromosomes 1, 9, 15, 16 and Y. Because, most of these chromosomes were implicated in the rearrangements, a detailed cytogenetic study was undertaken. This study included in situ hybridization of the satellite and alphoid DNAs of chromosomes 1, 9, 16 and Y combined with various chromosome banding methods (DA-DAPI, quinacrine mustard and R-banding). The data obtained, demonstrated that the breakpoints were always located outside the areas containing the satellite and alphoid DNAs. The situation observed here differs from that reported in breast cancers for which a high proportion of the breakpoints occur within these areas. These findings suggest that in glioblastoma, chromosome rearrangements result from different mechanisms than those implicated in breast cancers. Thus, in cancers, chromosomal instabilities may result from several mechanisms.

Azacitidine↗

PubMed1994

Oncogene amplification in human gliomas: a molecular cytogenetic analysis.

Nine cases of malignant gliomas were selected for the presence of double minutes (dmin) or homogeneously staining regions (hsr) detected by conventional cytogenetics. Analyses were performed on fresh (2 cases) or xenografted (5 cases) tumors or both (2 cases). A modified comparative genomic hybridization technique (mCGH) was applied exhibiting a single amplified locus in 8 tumors and 4 amplified loci in one tumor. Recurrent sites of amplification were detected in 7p11-p12 (5 cases) and 1q32.1 (2 cases). Signals were also observed in 4q11-q12, 5p15.1, 7q31, 8q24.1 and 9p2 in one tumor each. Southern blotting demonstrated that the genes for EGFR (epidermal growth factor receptor), PDGFRA (platelet derived growth factor receptor alpha), MET and MYC oncogenes were involved in 7p11-p12, 4q11-q12, 7q31 and 8q24.1 amplifications, respectively. These amplifications were found by in situ hybridization on tumor spreads, in dmin or episomes for EGFR, dmin for PDGFRA and MET, and hsr and dmin for MYC genes. Other mCGH signals, for which no target genes could be proposed, were confirmed by chromosome paintings on tumor metaphases. In one of the tumors, the coamplification of DNA from 5p15.1 and 9p2 bands in the same dmin was demonstrated.

Adult↗

PubMed1993

Definition and spatial location of mouse interleukin-2 residues that interact with its heterotrimeric receptor.

The high affinity receptor for interleukin-2 (IL-2) contains three subunits called IL-2R alpha, beta and gamma. A biological and receptor binding analysis based on 1393 different mutant mouse IL-2 (mIL-2) proteins was used to define the function of each of the 149 residues. By this genetic analysis, 44 residues were assigned important functions, 21 of which were structural. The remaining 23 residues consisted of 19 residues, from three separate regions, that were important for IL-2R alpha interaction; three residues, from two separate regions, that were important for IL-2R beta interaction; and a single residue important for IL-2R gamma interaction. We built a model mIL-2 structure based on the homologous human IL-2 (hIL-2) crystal structure. The roles of the 21 residues presumed to be important for structure were consistent with the model. Despite discontinuity in the primary sequence, the residues specific for each IL-2R subunit interaction were clustered and located to three disparate regions of the tertiary mIL-2 structure. The relative spatial locations of these three surfaces are different from the two receptor binding sites known for the structurally related human growth hormone and the significance of this observation is discussed.

Amino Acid Sequence↗

PubMed1993

An interleukin 4 (IL-4) mutant protein inhibits both IL-4 or IL-13-induced human immunoglobulin G4 (IgG4) and IgE synthesis and B cell proliferation: support for a common component shared by IL-4 and IL-13 receptors.

Interleukin 4 (IL-4) and IL-13 share many biological functions. Both cytokines promote growth of activated human B cells and induce naive human surface immunoglobulin D+ (sIgD+) B cells to produce IgG4 and IgE. Here we show that a mutant form of human IL-4, in which the tyrosine residue at position 124 is replaced by aspartic acid (hIL-4.Y124D), specifically blocks IL-4 and IL-13-induced proliferation of B cells costimulated by anti-CD40 mAbs in a dose-dependent fashion. A mouse mutant IL-4 protein (mIL-4.Y119D), which antagonizes the biological activity of mouse IL-4, was ineffective. In addition, hIL-4.Y124D, at concentrations of up to 40 nM, did not affect IL-2-induced B cell proliferation. hIL-4.Y124D did not have detectable agonistic activity in these B cell proliferation assays. Interestingly, hIL-4.Y124D also strongly inhibited both IL-4 or IL-13-induced IgG4 and IgE synthesis in cultures of peripheral blood mononuclear cells, or highly purified sIgD+ B cells cultured in the presence of anti-CD40 mAbs. IL-4 and IL-13-induced IgE responses were inhibited > 95% at a approximately 50- or approximately 20-fold excess of hIL-4.Y124D, respectively, despite the fact that the IL-4 mutant protein had a weak agonistic activity. This agonistic activity was 1.6 +/- 1.9% (n = 4) of the maximal IgE responses induced by saturating concentrations of IL-4. Taken together, these data indicate that there are commonalities between the IL-4 and IL-13 receptor. In addition, since hIL-4.Y124D inhibited both IL-4 and IL-13-induced IgE synthesis, it is likely that antagonistic mutant IL-4 proteins may have potential clinical use in the treatment of IgE-mediated allergic diseases.

Antigens, CD↗

PubMed1993

Receptors for interleukin-13 and interleukin-4 are complex and share a novel component that functions in signal transduction.

Interleukin-4 (IL-4) and interleukin-13 (IL-13) are two cytokines that are secreted by activated T cells and have similar effects on monocytes and B cells. We describe a mutant form of human interleukin-4 (hIL-4) that competitively antagonizes both hIL-4 and human interleukin-13 (hIL-13). The amino acid sequences of IL-4 and IL-13 are approximately 30% homologous and circular dichroism (CD) spectroscopy shows that both proteins have a highly alpha-helical structure. IL-13 competitively inhibited binding of hIL-4 to functional human IL-4 receptors (called hIL-4R) expressed on a cell line which responds to both hIL-4 and IL-13. Binding of hIL-4 to an hIL-4 responsive cell line that does not respond to IL-13, and binding of hIL-4 to cloned IL-4R ligand binding protein expressed on heterologous cells, were not inhibited by IL-13. hIL-4 bound with approximately 100-fold lower affinity to the IL-4R ligand binding protein than to functional IL-4R. The mutant hIL-4 antagonist protein bound to both IL-4R types with the lower affinity. The above results demonstrate that IL-4 and IL-13 share a receptor component that is important for signal transduction. In addition, our data establish that IL-4R is a complex of at least two components one of which is a novel affinity converting subunit that is critical for cellular signal transduction.

Amino Acid Sequence↗

PubMed1993

Experimental carcinomatous plexopathy.

To understand the pathophysiology of carcinomatous plexopathy better, we studied nerve lesions induced by an experimental thyroid carcinoma implanted over the brachial plexus in 30 Fisher rats. We performed a morphological study including light and electron microscopic examination and teased fibre preparations of brachial plexuses from implanted and control animals. The control side was normal in all. A large tumour always grew within 2 months in all implanted animals and a third of the rats eventually developed weakness of the corresponding anterior limb extremity. On gross examination the tumour always surrounded the brachial plexus, which showed a variety of microscopic abnormalities, ranging from isolated endoneurial oedema to total degeneration of nerve fibres in 41% of the implanted rats. The most frequent lesions consisted of segmental demyelination associated with endoneurial oedema at the site of compression. Some axons degenerated distally and regeneration by sprouting of the proximal stump was noted 80 days after implantation. All subpopulations of nerve fibres were equally affected. Invasion of the intrafascicular area by the tumour was an uncommon finding, in comparison with the constant entrapment of the branches of the plexus by the tumour. This invasion by the tumour induced demyelination of nerve fibres at the site of compression, and sometimes at a distance from the tumour. Regeneration did not occur when the tumour had invaded the intrafascicular area.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Hypersensitivity to latex, chestnut, and banana.

The incidence of latex-allergic patients is probably higher than suspected. A spectrum of IgE-dependent allergic reactions to latex products including urticaria, rhinitis, asthma, angioedema, and life-threatening anaphylaxis has been increasingly reported in recent years. We describe three patients with rubber hypersensitivity and allergy to fruit (banana and chestnut). Immediate positive responses were obtained in prick tests with latex, banana, and chestnut extracts. Histamine release was positive and specific IgE antibodies to all three extracts were detected by fluorescence radioimmunoassay. In the RAST-inhibition studies, the extract of latex inhibited the binding of chestnut and banana, but chestnut and banana extracts did not inhibit the binding of latex. These results suggest a sensitivity to crossreacting antigens in latex allergy associated with allergy to certain fruits.

Adult↗

PubMed1993

[Prevalence of fascioliasis in humans, horses, pigs, and wild rabbits in 3 Chilean provinces].

This study sought to estimate for the first time the prevalence of fascioliasis among the rural population in the Chilean provinces of Curico, Talca, and Linares, while also determining the disease's prevalence among horses and wild rabbits in Curico and Talca and among pigs in Talca. From January 1986 to December 1990 a randomly selected sample of 5,861 persons in the three provinces was given intradermal, complement-fixation, double-diffusion, and immunoelectrophoresis tests to detect antibody to Fasciola hepatica. In addition, the ELISA test was used in Talca and Linares. Fecal specimens from horses and pigs were inspected for eggs, and the liver and bile ducts of rabbits were examined histopathologically. The overall prevalence of infection among the human subjects was 0.70%, with rates of 0.6% in Curico, 0.75% in Talca, and 0.71% in Linares. The prevalences of infection in horses, rabbits, and pigs were 13.5%, 6.1%, and 20.6%, respectively. It is estimated that some 2,000 people are infected in the study area. It is recommended that rabbits be taken into account in all control programs for this zoonosis.

Adolescent↗

PubMed1992

[Neurologic syndromes associated with anti-Hu antibody. Study of 24 patients].

BACKGROUND: Twenty-four patients with neurologic involvement and anti-Hu antibodies were studied with the aim of defining the type of tumor associated, evaluating whether the clinico-pathologic picture agreed with the concept of paraneoplastic encephalomyelitis (PEM) and evaluating the treatments used. METHODS: The study was retrospective with the clinical histories being reviewed to define the neurologic syndromes, their evolution and response to the different treatments, time of appearance and type of tumor as well as the neuropathologic changes in the patients undergoing autopsy. RESULTS: In 18 patients a neoplasm was diagnosed as small cell pulmonary carcinoma (SCPC) in 89% of the cases. The neurologic picture preceded the tumor by an average of five months. The clinical pictures included: sensitive neuropathy (20 patients), cerebellous and truncus encephalicus involvement (8 patients), motor neuropathy (6 patients), cortical involvement (5 patients) and neurovegetative dysfunction (4 patients). In 55% of the patients more than one area was altered. Post mortem studies carried out on 5 patients demonstrated inflammatory infiltrates and neuronal loss in multiple areas of the nervous system. None of the patients improved with treatment. The 9 patients who only received immunodepressants evolved in a way similar to those who were not treated. In 7 of the 11 patients who received antitumoral therapy, the neurologic syndrome stabilized for at least 6 months. CONCLUSIONS: The clinicopathological picture and the associated tumor seen in patients with anti-Hu antibodies are identical to those seen in PEM. Antitumoral treatment seems to be more effective than immunodepressant treatment.

Adult↗

PubMed1992

Treatment of malignant gliomas with surgery, intraarterial chemotherapy with ACNU and radiation therapy.

Forty patients with malignant supratentorial gliomas received iterative intraarterial (IA) infusions of ACNU, 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea at a dose of 150 mg repeated every 6 weeks. Group A consisted of eighteen patients previously treated with surgery, radiation therapy (RT) and sometimes chemotherapy, who received IA ACNU at tumor recurrence. Group B consisted of twenty two patients who received IA ACNU in the postoperative pre-RT period. In group A, 8/18 patients (44%) had an objective response, including 6/12 anaplastic astrocytomas (AA) and 2/6 glioblastoma multiforme (GBM), while 10/18 patients (56%) did not respond. Median survival time was 6 months for GBM and 12 months for AA. In group B, 6/22 patients (27%) had an objective response (4/18 GBM and 2/4 AA) and 16/22 patients (73%) did not respond. Nine patients had such an extensive tumor after one or two courses of IA ACNU that RT was cancelled. Median survival time was 8 months for GBM and 8 months for AA. Three patients (8%) had ophthalmologic toxicity on the infused side. There was no case of leukoencephalopathy.

Adult↗

PubMed1992

Plasmapheresis and antineoplastic treatment in CNS paraneoplastic syndromes with antineuronal autoantibodies.

We retrospectively evaluated the effect of plasmapheresis (PE) in seven patients with paraneoplastic encephalomyelitis (PEM), small-cell lung carcinoma, and anti-Hu antibodies, and four patients with paraneoplastic cerebellar degeneration (PCD), ovarian or breast cancer, and anti-Yo antibodies. In addition to PE, patients received prednisone (nine), cyclophosphamide (eight), or treatment of the tumor (five). All but one patient were severely disabled by the time PE began. The clinical outcome was compared with that of five patients (PEM, four; PCD, one) who only had treatment of the tumor. Only one of these five patients had a severe neurologic deficit at the onset of the antineoplastic treatment. No patient improved. Two patients treated with PE and antineoplastic therapy and three who only received treatment of the tumor remained stable for at least 6 months. Four of the five patients with a stable course started the treatment when the neurologic deficit was not severe. We conclude that the efficacy of PE with other immunosuppressive therapies in the stabilization of the neurologic deficit is uncertain.

Aged↗

PubMed1992

[Fascioliasis in populations of rural areas with high prevalence of animal infection].

Between January 1986 and December 1990 the prevalence of F. hepatica infection was studied in 5861 rural inhabitants of the provinces of Curico, Talca and Linares, VII Region, an hyperendemic zone of animal fascioliasis. Every one was screened by intradermal (IDR), complement fixation (CF), double diffusion (DD) counterelectrophoresis (CIEF), immunoelectrophoresis (IEP) and enzyme-linked immunoabsorbent assay (ELISA) tests. 366/1881 (9.3%) had positive IDR; 61 (1.04%) positive CF; 14 (0.24%) positive DD and 105/3838 (2.73%) positive ELISA and thus considered under suspicion to be infected. F. hepatica eggs were searched in stool in 241 of these persons. 37 cases were thus confirmed. Another 4 individuals with positive immunobiological tests and absence of the parasite eggs in stools were confirmed by duodenal intubation. 21 of the confirmed cases (51.2%) had less than 15 years of age. Women were more frequently infected than men (73.2% vs 26.8%). The 41 cases represent 0.7% of the surveyed population predicting 2000 cases among the total rural population of these provinces (300,000 persons). These results indicate that human fascioliasis is an important problem in the zone, perhaps much higher if family contacts of the index cases and symptomatic persons are included.

Adolescent↗

PubMed1992

[Chromosome abnormalities and adenine metabolism in human glial tumors].

Most chromosome aberrations in gliomas are numerical, resulting in either gains or deficiencies of whole chromosomes. In tumors of low malignancy, the karyotype is frequently normal or exhibits a loss of sex chromosome and a gain of chromosome 7. These two anomalies may not be directly related to malignancy. In the highly malignant cases, the two most frequent aberrations are the gain of chromosome 7 and the loss of chromosome 10, other anomalies such as losses or deletions of chromosomes, 9, 22, 6, 13 and 14 being detected at various frequencies. Several of these chromosomes carry important genes of adenine metabolism: AK1 and AK3 (adenylate kinase) and MTAP (methylthioadenosine phosphorylase) for chromosome 9; ADK (adenosine kinase) and mitochondrial ATPase for chromosome 10; ADSL (adenylosuccinate lyase) for chromosome 22, NP (nucleoside phosphorylase) for chromosome 14. We performed the corresponding assays of enzyme activity on both fresh tumors and tumors grafted on nude mice, which showed that these enzymes had a relatively low activity although the tumors were proliferating. However, chromosome losses do not seem to directly cause the metabolic alterations by gene dosage effect. Interestingly, chromosome 10, frequently deficient, also carries genes of importance for glycolysis (hexokinase) and glutamate metabolism (glutamate dehydrogenase and glutamate oxaloacetate transaminase). The deficiency for these genes could be taken into account for a better type of chemotherapy by antimetabolics.

Adenine↗

PubMed1991

[Autoimmunity and paraneoplastic neurologic syndromes].

Paraneoplastic syndromes affecting the nervous system are rare and their diagnosis is often difficult when the original cancer is unknown. Recently, high levels of antineuronal antibodies (AB) have been found in serum and CSF of some patients with paraneoplastic syndromes. The anti-Yo AB recognizes 2 proteins of 34 and 62 kd in the cytoplasm of Purkinje cells and in malignant cells of patients suffering from paraneoplastic cerebellar degeneration associated with ovarian and breast cancer. The anti-Hu AB recognizes a 37-40 kd protein in nuclei of neurons and in tumor cells of patients suffering from subacute sensory neuronopathy and encephalomyelitis associated with small cell lung cancer. Other antineuronal AB have been more rarely identified. The presence of high titer of one of these AB in a patient with suspected paraneoplastic syndrome is of great practical interest since it confirms the neurological diagnosis and strongly suggests the location of the primary tumor when the malignancy is unknown. The pathogenetic role of the antineuronal AB is unknown but it is likely that some paraneoplastic syndromes affecting the nervous system are due to an immune reaction against antigens shared by the tumor and the nervous system. To date, no efficient treatment has been found.

Autoantibodies↗

PubMed1990

Reappraisal of the effect of Ca2+ on the activity of liver microsomal glucose-6-phosphatase.

It has recently been reported that free Ca2+, a second hormonal messenger in the liver, can modulate the activity of liver glucose-6-phosphatase by inhibition (van de Werve, G. (1989) J. Biol. Chem. 264, 6033-6036) or activation (Yamagushi, M., Mori, S., and Suketa, Y. (1989) Chem. Pharm. Bull. (Tokyo) 37, 388-390). Such a controversial role for Ca2+ is reinvestigated by comparing the effect of the addition of free Ca2+ (10(-10) to 20.10(-3) M) under the form of CaCl2 or of Ca-EGTA buffers. We show that the glucose-6-phosphatase activity is: 1) increased in the presence of CaCl2 at concentrations higher than 10(-4) M and unaffected in the presence of CaCl2 at lower concentrations; 2) decreased in the presence of Ca-EGTA buffers yielding free Ca2+ concentrations higher than 10(-8) M; 3) the latter effect is not depending on free Ca2+ or free EGTA concentrations, but on Ca.EGTA complex concentration. In addition, these effects can be reproduced in the same concentration ranges by MgCl2 and Mg-EDTA buffers, respectively. It is concluded that a physiological role for free Ca2+ on the activity of liver glucose-6-phosphatase remains to be established.

Animals↗

PubMed1990

[Cerebral hemorrhage associated with the use phenylpropanolamine].

Phenylpropanolamine is a sympatheticomimetic agent which is widely used in pharmacologic preparations to treat nasal congestion, and to produce and anorexigenic or stimulant action. In the last years complications affecting the nervous system or the general condition have been reported. There is still controversy with regard to the safety of this pharmacologic agent. In this study we report two cases of parenchymal cerebral hemorrhage secondary to phenylpropanolamine administration. In the second case we observed angiographic findings of a reversible vasculopathy.

Adult↗

PubMed1989

Vasoactive intestinal peptide stimulates long-chain fatty acid oxidation and inhibits acetyl-coenzyme A carboxylase activity in isolated rat enterocytes.

The effects of vasoactive intestinal peptide (VIP) on fatty acid oxidation in isolated rat enterocytes were investigated. VIP (10(-7) M) increased more than 2-fold the production of 14CO2 from [U-14C]palmitate. This effect was dose-dependent (K0.5 = 5.10(-11) M) and appeared to be related to the stimulation of cAMP production since it was mimicked by forskolin (10(-4) M). VIP also stimulated oxygen consumption of the cells, an effect accounted for by the stimulation of the oxidation of both exogenous added palmitate (0.12 mM) and endogenous fatty acids produced by lipolysis. VIP appeared to specifically enhance the oxidation of long-chain fatty acids since its effects were counteracted by 5.10(-5) M sodium 2-[6-(chlorophenoxy)hexyl]oxirane-2-carboxylate, a potent inhibitor of carnitine palmitoyltransferase 1, and since VIP did not affect cell respiration in the presence of octanoate. These results suggested that VIP stimulated long-chain fatty acid oxidation by increasing their translocation into the mitochondria. Therefore, we examined the effect of VIP on the activity of acetyl-coenzyme A carboxylase, the enzyme responsible for the biosynthesis of malonyl-CoA, a physiological inhibitor of carnitine acyltransferase 1. VIP produced an acute, dose-dependent (Ki = 3.10(-11) M), 90% inhibition of acetyl-coenzyme A carboxylase activity. These results allow us to elucidate the mechanism of the recently reported inhibitory effect of VIP on glucose oxidation (Vidal, H., Comte, B., Beylot, M., and Riou, J. P. (1988) J. Biol. Chem. 263, 9206-9211) and demonstrate for the first time that balance between fatty acids and glucose as energetic fuels is under neurohormonal control in isolated rat enterocytes.

Acetyl-CoA Carboxylase↗

PubMed1989

Acute hemichorea due to infarction in the corona radiata.

A 66-year-old hypertensive man presented with acute hemichorea. Magnetic resonance imaging disclosed an infarct, confined to the contralateral corona radiata, that interrupted excitatory corticostriate fibres. The movement disorder may have been caused by subcortical lesion without direct involvement of the basal ganglia.

Acute Disease↗