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Biomedical subjects

A Gonzalez

Publications and source records attributed to A Gonzalez.

At least 253 records · Page 14Linked to original sources

Sorting and endocytosis of viral glycoproteins in transfected polarized epithelial cells.

Previous studies (Rindler, M. J., I. E., Ivanov, H. Plesken, and D. D. Sabatini, 1985, J. Cell Biol., 100: 136-151; Rindler, M. J., I. E. Ivanov, H. Plesken, E. J. Rodriguez-Boulan, and D. D. Sabatini, 1984, J. Cell Biol., 98: 1304-1319) have demonstrated that in polarized Madin-Darby canine kidney cells infected with vesicular stomatitis virus (VSV) or influenza virus the viral envelope glycoproteins G and HA are segregated to the basolateral and apical plasma membrane domains, respectively, where budding of the corresponding viruses takes place. Furthermore, it has been shown that this segregation of the glycoproteins reflects the polarized delivery of the newly synthesized polypeptides to each surface domain. In transfection experiments using eukaryotic expression plasmids that contain cDNAs encoding the viral glycoproteins, it is now shown that even in the absence of other viral components, both proteins are effectively segregated to the appropriate cell surface domain. In transfected cells, the HA glycoprotein was almost exclusively localized in the apical cell surface, whereas the G protein, although preferentially localized in the basolateral domains, was also present in lower amounts, in the apical surfaces of many cells. Using transfected and infected cells, it was demonstrated that, after reaching the cell surface, the G protein, but not the HA protein, undergoes interiorization by endocytosis. Thus, in the presence of chloroquine, a drug that blocks return of interiorized plasma membrane proteins to the cell surface, the G protein was quantitatively trapped in endosome- or lysosome-like vesicles. The sequestration of G was a rapid process that was completed in many cells by 1-2 h after chloroquine treatment. The fact that in transfected cells the surface content of G protein was not noticeably reduced during a 5-h incubation with cycloheximide, a protein synthesis inhibitor that did not prevent the effect of chloroquine, implies that normally, G protein molecules are not only interiorized but are also recycled to the cell surface.

Animals↗

Effects of fish meal as source of protein on intestinal maltase activity and intestinal and renal leucine aminopeptidase activity of growing rats.

The effect of high-protein fish meal on maltase and leucine aminopeptidase (LAPase) activities of the intestinal mucosa as well as the renal LAPase activity was studied. Four groups of female Wistar rats, weighing between 40-60 g, were fed diets with a 4 or 12% protein content of dry matter for 25 days. The protein source was casein for the control groups and fish meal derived from Coryphaenoides rupestris for the test groups. The results show a decrease (p less than 0.005) in intestinal maltase and LAPase activities and renal LAPase activity in animals fed with 12% of fish meal protein compared to those fed with casein, while the rats fed 4% of fish meal protein showed a decrease in intestinal maltase activity and no significant difference in LAPase activity compared with the control group. These results seem to indicate that the intestinal maltase is influenced by the quality and quantity of dietary protein, while the intestinal and renal LAPase activity is only changed by the quality of protein.

Animals↗

Bronchopulmonary dysplasia in the tiny infant.

Bronchopulmonary dysplasia, defined as ventilator or oxygen dependence accompanied by characteristic x-ray changes, occurs frequently in the tiny baby. The authors report their own experience in a large metropolitan hospital. A review of etiologic factors and therapeutic interventions for bronchopulmonary dysplasia in tiny infants is detailed.

Adrenal Cortex Hormones↗

Apparent generation of a segmented mRNA from two separate tandem gene families in Trypanosoma cruzi.

Using a cDNA for an abundant Trypanosoma cruzi mRNA as probe, we have cloned and sequenced a gene which is organized in at least 20 nearly perfect tandem repeats of 940 base pairs. The 5' end of the mRNA has been sequenced by primer extension and found to contain a 35 nucleotide mini-exon (or spliced-leader) sequence that is ubiquitous in trypanosome mRNAs. This sequence, however, is not present in the tandem genomic repeats which encode the exon containing the major portion of the mRNA. Previous studies have shown that the 35-nucleotide sequence is encoded by a separate tandem gene family. One model to explain the formation of a segmented mRNA invokes priming of transcription by a small RNA which contains the leader sequence at its 5' end. However, northern blot analysis of total trypanosome RNA reveals a ladder of molecules larger than the mature mRNA, which appear to be faithful multimeric copies of the tandem gene. The discrete sizes of these RNAs correspond to those expected for partially processed precursors. These observations lend credence to the possibility of an alternative model where segmented mRNAs are generated by inter-molecular splicing.

Animals↗

Antigen-specific lymphocyte transformation in congenital toxoplasmosis.

Secreted (TSA) and water lysed antigens (WLA) derived from cell culture of the RH strain of Toxoplasma gondii have been used to induce antigen-specific mitogenesis of lymphocytes from children with congenital toxoplasmosis. Responsiveness to WLA was variable, with all patients giving false negative results. Responses to TSA, however, were highly specific, with no false negatives. This increased specificity was not due to an increased response to TSA (P less than 0.001), but a lower TSA response by the lymphocytes of the uninfected subjects (P greater than 0.1), compared with WLA in both cases. Preliminary studies have shown that while WLA induces high levels of non-specific immunity, such as natural killing, TSA is able to induce specific killing of Toxoplasma in vitro through the action of activated macrophages; this may partially explain the increased specificity of TSA in the lymphocyte transformation test.

Adult↗

Biosynthesis and intracellular sorting of growth hormone-viral envelope glycoprotein hybrids.

Various aspects of the biogenetic mechanisms that are involved in the insertion of nascent plasma membrane proteins into the endoplasmic reticulum (ER) membrane and their subsequent distribution through the cell have been investigated. For these studies chimeric genes that encode hybrid proteins containing carboxy-terminal portions of the influenza virus hemagglutinin (154 amino acids) or the vesicular stomatitis virus envelope glycoprotein (G) (60 amino acids) linked to the carboxy terminus of a nearly complete secretory polypeptide, growth hormone (GH), were used. In in vitro transcription-translation experiments, it was found that the insertion signal in the GH portion of the chimeras led to incorporation of the membrane protein segments into the ER membrane. Effectively, GH became part of the luminal segment of membrane proteins of which only very small segments, corresponding to the cytoplasmic portions of the G or HA proteins, remained exposed on the surface of the microsomes. When the chimeric genes were expressed in transfected cells, the products, as expected, failed to be secreted and remained cell-associated. These results support the assignment of a halt transfer role to segments of the membrane polypeptides that include their transmembrane portions. The hybrid polypeptide containing the carboxy-terminal portion of HA linked to GH accumulated in a juxtanuclear region of the cytoplasm within modified ER cisternae, closely apposed to the Golgi apparatus. The location and appearance of these cisternae suggested that they represent overdeveloped transitional ER elements and thus may correspond to a natural way station between the ER and the Golgi apparatus, in which further transfer of the artificial molecules is halted. The GH-G hybrid could only be detected in transfected cells treated with chloroquine, a drug that led to its accumulation in the membranes of endosome or lysosome-like cytoplasmic vesicles. Although the possibility that the chimeric protein entered such vesicles directly from the Golgi apparatus cannot be ruled out, it appears more likely that it was first transferred to the cell surface and was then internalized by endocytosis.

Animals↗

Pericarditis in infective endocarditis.

Three patients with infective endocarditis who presented with severe precordial pain and pericardial rubs are described in whom sterile pericardial and pleural effusions were found. The pericardial pain disappeared and the effusions regressed with successful antibiotic treatment. A similar mechanism to the postmyocardial infarction syndrome is suggested.

Adult↗

Physiological model for distribution of sulfathiazole in swine.

A physiological flow model was developed for the distribution of sulfathiazole residues in various tissues in swine. The approach was compartmental, in which the compartments and equilibrium constants had physiological meaning. Differential equations were developed, and appropriate parameter values and initial conditions were substituted and solved by a fourth-order Runga-Kutta technique. Simulation values corresponded with the experimentally determined concentration values in plasma and kidney, liver, muscle, fat, and heart tissues.

Animals↗

Cerebellar connections in Xenopus laevis. An HRP study.

In the present study the cerebellar afferents in the clawed toad Xenopus laevis have been analysed with the horseradish peroxidase (HRP) technique. In addition, data on the efferent connections of the cerebellum could be gathered, based on the phenomenon of anterograde transport of HRP. Cerebellar afferents in Xenopus laevis appear to arise mainly in the vestibular nuclear complex, in a primordial inferior olive and in the spinal cord. Both primary (arising in the ipsilateral vestibular ganglion) and secondary vestibulocerebellar projections were found. A distinct crossed olivocerebellar projection to the molecular layer of the cerebellum was found. Two spinocerebellar pathways are present in Xenopus laevis, as in other anurans, viz. an ipsilateral dorsal spinocerebellar tract, presumably arising in dorsal root ganglion cells, and a larger ventral pathway, bilaterally arising in the spinal gray matter. The latter tract mainly originates in the ventrolateral and ventromedial spinal fields. Furthermore, a secondary trigeminocerebellar projection arising in the descending trigeminal nucleus, a cerebellar projection arising in the dorsal column nucleus, a small projection arising in a possible primordium of the mammalian nucleus prepositus hypoglossi, a raphecerebellar projection, and a small cerebellar projection originating in the ipsilateral mesencephalic tegmentum were demonstrated. Cerebellar efferents in Xenopus laevis are mainly aimed at the vestibular nuclear complex. A distinct ipsilateral cerebellovestibular projection present throughout the vestibular nuclear complex presumably arises in Purkyn ĕ cells, a smaller contralateral projection in the cerebellar nucleus. In addition, a small primordial brachium conjunctivum, projecting to the red nucleus, was noted. The basic pattern of cerebellar connections as suggested for terrestrial vertebrates (ten Donkelaar and Bangma 1984) is also found in the permanently aquatic anuran Xenopus laevis.

Animals↗

Familial agenesis of the corpus callosum with hypothermia and apneic spells.

Two siblings, a boy and a girl, with agenesis of the corpus callosum, apneic spells, attacks of apnea, cyanosis and spontaneous hypothermia, are reported about. Both children died after a few months of life. Postmortem examination revealed a severe spongiosis of the white matter in addition to the agenesis of the corpus callosum and septum pellucidum, in both cases.

Agenesis of Corpus Callosum↗

Minichromosomal repetitive DNA in Trypanosoma cruzi: its use in a high-sensitivity parasite detection assay.

We have isolated genomic clones containing members of a tandemly repeated DNA family from Trypanosoma cruzi. This family, which contains a 195-base pair (bp) repeating unit, is the most abundant repetitive DNA in this organism. DNA sequencing analysis of three adjacent tandem repeats as well as two independent nonadjacent repeats showed relatively little sequence heterogeneity. Surprisingly, the three tandem elements contained a 585-bp open reading frame. However, blot hybridization of RNA from epimastigotes as well as blood-form trypomastigotes failed to show evidence for transcription of these sequences. Fractionation of whole T. cruzi DNA in sucrose gradients or in agarose gels followed by hybridization with appropriate radioactive probes showed that the size distribution of DNA bearing the 195-bp repetitive element is distinct from that of kinetoplast DNA as well as from that of DNA bearing tubulin genes. Hybridization of the 195-bp element probe with DNA from six different T. cruzi strains was positive; hybridization with DNA of other protozoa was negative with the single exception of Leptomonas collosoma , which displayed a weak cross-hybridization signal. Clones bearing this repetitive element are shown to be useful as probes for identification and counting of T. cruzi cells by dot-blot hybridization. The sensitivity of this assay permits detection of the DNA of 30 parasites in blood samples.

Base Sequence↗

Cross sectional echocardiographic assessment of the aortic root and coronary ostial stenosis in familial hypercholesterolaemia.

Aortic root abnormalities (atherosclerotic thickening and obstruction) seen at necropsy may readily be detected by aortography in familial hypercholesterolaemia. We studied 35 patients with familial types IIa and IIb hyperlipoproteinaemia including three homozygotes and 32 heterozygotes. Two homozygotes showed abnormal bright echoes (atheroma) encircling the proximal aortic root, which interfered with full excursion of the aortic cusps. One homozygote showed the typical echocardiographic features of supravalvular aortic stenosis at the superior border of the sinus of Valsava with normal aortic cusps. Cardiac catheterisation showed valvular gradients of 15 and 80 mm Hg in two homozygotes and a supravalvular gradient of 40 mm Hg in the third. Left coronary artery ostial stenosis was identified by echocardiography in all three homozygotes. Echocardiographic measurements of the aortic root in the 32 heterozygotes were similar to the control group, but 10 patients showed abnormal bright echoes within the aortic cusps and four had supravalvular changes similar to, but less severe than, the homozygotes. In one severely heterozygote supravalvular atheroma prevented full aortic cusp excursion, and this finding was confirmed during coronary artery bypass surgery.

Adolescent↗

Amphetamine, haloperidol, and experience interact to affect rate of recovery after motor cortex injury.

Rats subjected to unilateral ablation of the motor cortex and placed on a narrow beam displayed transient contralateral paresis. An immediate and enduring acceleration of recovery was produced by a single dose of d-amphetamine given 24 hours after injury. This effect was blocked by haloperidol or by restraining the animals for 8 hours beginning immediately after amphetamine administration. A single dose of haloperidol given 24 hours after injury markedly slowed recovery. This effect was also blocked by restraining the animals.

Animals↗