Multidisciplinary approach in the treatment of complex cases.
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Adolescent↗
Biomedical subjects
J M Gonzalez
Publications and source records attributed to J M Gonzalez.
Ibuprofen, aspirin and acetaminophen toxicosis and treatment in dogs and cats.
Toxicosis to 3 commonly available analgesics--ibuprofen, aspirin and acetaminophen--occurs in dogs and cats after acute ingestion or repetitive administration of therapeutic or excessive doses. Whereas in acute exposure, where the clinical course of an overdose to all 3 drugs is predictable in relation to the amount ingested, in chronic exposure to therapeutic doses of aspirin and ibuprofen, the development of gastric ulcers and analgesic nephropathy is unpredictable. Ibuprofen is not recommended for prolonged treatment in dogs and cats due to the likelihood of ulcer formation. Although gastric mucosal adaptation usually occurs with repeated therapeutic doses of aspirin, some individuals nevertheless develop gastric ulcers; simultaneous administration of the prostaglandin analogue misoprostol can reduce the risk. Following acute ingestion of aspirin or ibuprofen, treatment is essentially symptomatic and supportive following early decontamination procedures. Gastrointestinal protectants and i.v. fluids with sodium bicarbonate are generally recommended. Acetaminophen toxicosis is usually associated with single acute ingestion, and the primary target organs affected are the liver and the red blood cells in dogs and cats respectively. Because signs can progress rapidly with acute acetaminophen overdose, administration of N-acetylcysteine is always recommended, even when the history is unclear. This report summarizes the common clinical presentations of dogs and cats exposed to therapeutic or excessive doses of ibuprofen, aspirin or acetaminophen, and describes the treatment procedures advised by the ASPCA-National Animal Poison Control Center.
Acetaminophen↗
Mapping and comparison of the B-cell epitopes recognized on the Plasmodium vivax circumsporozoite protein by immune Colombians and immunized Aotus monkeys.
Plasma samples of individuals from two malaria-endemic villages on the Colombian Pacific coast and synthetic peptides representing different fragments of the central and flanking regions of the Plasmodium vivax circumsporozoite protein (CSP) were used to perform a fine mapping of the B-cell epitopes on the whole CSP. In addition, the immunogenicity of long polypeptides corresponding to the amino (N) and carboxyl (C) regions was evaluated in Aotus monkeys. The epitopes recognized after natural infection of humans and after immunization of Aotus with these synthetic peptides were compared. Human samples more frequently contained specific antibodies to the central region. The type-I repeat region of the CSP was predominantly recognized by the human sera (by 68% of those from the village of Zacarías and 75% of those from Bajo Calima), a significantly smaller population reacting with the type-II repeat (20% and 11%, respectively). Most of the sera reacting with the type-I repeat recognized the minimal epitope AGDR. Although the N- and C-terminal polypeptides were both highly immunogenic in Aotus and induced long-lasting antibodies, titres of antibodies to the C-terminal polypeptide were higher than those of antibodies to the N-terminal. Competitive inhibition assays performed using human and monkey plasma allowed the identification of dominant B-cell epitopes on sequence 71-90 (p8) from the amino region and sequence 332-361 (p24/p25) from the carboxyl region. The high prevalence of naturally induced antibodies to the three epitopes, the possible functional role of the corresponding sequences, and the high immunogenicity of these epitopes in Aotus could be of great importance in the development of a malaria vaccine based on P. vivax CSP.
Adult↗
Pressure and temperature effects on growth and viability of the hyperthermophilic archaeon Thermococcus peptonophilus.
We studied the effects of high temperatures and elevated hydrostatic pressures on the physiological behavior and viability of the extremely thermophilic deep-sea archaeon Thermococcus peptonophilus. Maximal growth rates were observed at 30 and 45 MPa although no significant increases in cell yields were detected. Growth at 60 MPa was slower. The optimal growth temperature shifted from 85 degrees C at 30 MPa to 90-95 degrees C at 45 MPa. Cell viability during the stationary phase was also enhanced under high pressure. A trend towards barophily at pressures greater than those encountered in situ at the sea floor was demonstrated at increasing growth temperatures. The viability of cells during starvation, at high temperature (90, 95 degrees C), and at low temperature (10 degrees C) was enhanced at 30 and 45 MPa as compared to atmospheric pressure. These results show that the extremely thermophilic archaeon T. peptonophilus is a barophile.
Adenosine Triphosphate↗
Perfusion deficit parallels exacerbation of cerebral ischemia/reperfusion injury in hyperglycemic rats.
Magnetic resonance imaging (MRI) techniques were used to determine the effect of preexisting hyperglycemia on the extent of cerebral ischemia/reperfusion injury and the level of cerebral perfusion. Middle cerebral artery occlusion (MCAO) was induced by a suture insertion technique. Forty one rats were divided into hyperglycemic and normoglycemic groups with either 4 hours of continuous MCAO or 2 hours of MCAO followed by 2 hours of reperfusion. Diffusion-weighted imaging (DWI) was performed at 4 hours after MCAO to quantify the degree of injury in 6 brain regions. Relative cerebral blood flow (CBF) and cerebral blood volume (CBV) were estimated using gradient echo (GE) bolus tracking and steady-state spin echo (SE) imaging techniques, respectively. Brain injury correlated with the perfusion level measured in both SE CBV and dynamic GE CBF images. In the temporary MCAO model, mean lesion size in DWI was 118% larger and hemispheric CBV was reduced by 37% in hyperglycemic compared with normoglycemic rats. Hyperglycemia did not significantly exacerbate brain injury or CBV deficit in permanent MCAO models. We conclude that preexisting hyperglycemia increases acute postischemic MRI-measurable brain cellular injury in proportion to an associated increased microvascular ischemia.
Animals↗
An unusual cause of cyanosis in a patient with a carcinoid tumor.
We report the second case of a right-to-left interatrial shunt due to a carcinoid tumor, which was successfully corrected by surgery. The patient had closure of a patent foramen ovale and tricuspid valve replacement. One and a half years after surgery, the patient had no symptoms related to heart disease.
Aged↗
Sagittula stellata gen. nov., sp. nov., a lignin-transforming bacterium from a coastal environment.
A numerically important member of marine enrichment cultures prepared with lignin-rich, pulp mill effluent was isolated. This bacterium was gram negative and rod shaped, did not form spores, and was strictly aerobic. The surfaces of its cells were covered by blebs or vesicles and polysaccharide fibrils. Each cell also had a holdfast structure at one pole. The cells formed rosettes and aggregates. During growth in the presence of lignocellulose or cellulose particles, cells attached to the surfaces of the particles. The bacterium utilized a variety of monosaccharides, disaccharides, amino acids, and volatile fatty acids for growth. It hydrolyzed cellulose, and synthetic lignin preparations were partially solubilized and mineralized. As determined by 16S rRNA analysis, the isolate was a member of the alpha subclass of the phylum Proteobacteria and was related to the genus Roseobacter. A signature secondary structure of the 16S rRNA is proposed. The guanine-plus-cytosine content of the genomic DNA was 65.0 mol%. On the basis of the results of 16S rRNA sequence and phenotypic characterizations, the isolate was sufficiently different to consider it a member of a new genus. Thus, a novel genus and species, Sagittula stellata, are proposed; the type strain is E-37 (= ATCC 700073).
Bacterial Adhesion↗
In situ reverse transcription, an approach to characterize genetic diversity and activities of prokaryotes.
Reverse transcription of RNA molecules inside intact bacterial cells was carried out by using reverse transcriptase with a single oligonucleotide complementary to specific 16S rRNA or mRNA sequences. Fluorescently labeled nucleotides were incorporated into each transcribed cDNA inside cells. This protocol is termed in situ reverse transcription (ISRT). In this study, by using species-specific primers targeting unique regions of the 16S rRNA sequences, ISRT was used successfully to detect and enumerate the two lignin-degrading bacteria Microbulbifer hydrolyticus IRE-31 and Sagittula stellata E-37 in culture mixtures and complex enrichment communities selected for lignin degradation. Image analysis revealed that M. hydrolyticus IRE-31 and S. stellata E-37 accounted for approximately 30 and 2%, respectively, of the total bacterial cells in lignin enrichment communities. Populations estimated by ISRT were comparable to those estimated by in situ hybridization (ISH) techniques and to those estimated by hybridization against extracted community DNA. ISRT was also successfully used to detect Pseudomonas putida F1 expressing the todC1 gene in seawater exposed to toluene vapor. ISRT provided a higher signal intensity than ISH, especially when targeting mRNA. The calculated pixel intensities resulting from ISRT were up to 4.2 times greater than those from ISH. This suggests that multiple incorporation of fluorescently labeled nucleotides into cDNA provides a high sensitivity for phylogenetic identification of bacterial populations as well as detection of cells expressing a specific functional gene within complex bacterial communities.
Journal Article↗
Diabetes mellitus update.
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Blood Glucose↗
Anion exchanger 1 (band 3) is required to prevent erythrocyte membrane surface loss but not to form the membrane skeleton.
The red blood cell (RBC) membrane protein AE1 provides high affinity binding sites for the membrane skeleton, a structure critical to RBC integrity. AE1 biosynthesis is postulated to be required for terminal erythropoiesis and membrane skeleton assembly. We used targeted mutagenesis to assess AE1 function in vivo. RBCs lacking AE1 spontaneously shed membrane vesicles and tubules, leading to severe spherocytosis and hemolysis, but the levels of the major skeleton components, the synthesis of spectrin in mutant erythroblasts, and skeletal architecture are normal or nearly normal. The results indicate that AE1 does not regulate RBC membrane skeleton assembly in vivo but is essential for membrane stability. We postulate that stabilization is achieved through AE1-lipid interactions and that loss of these interactions is a key pathogenic event in hereditary spherocytosis.
Animals↗
Ankyrin-1 mutations are a major cause of dominant and recessive hereditary spherocytosis.
Hereditary spherocytosis (HS) is the most common inherited haemolytic anaemia in Northern Europeans. The primary molecular defects reside in the red blood cell (RBC) membrane, particularly in proteins that link the membrane skeleton to the overlying lipid bilayer and its integral membrane constituents. Ankyrin-1 is the predominant linker molecule. It attaches spectrin, the major skeletal protein, to the cytoplasmic domain of band 3, the RBC anion exchanger. Two-thirds of patients with HS have combined spectrin and ankyrin-1 deficiency; deficiency of band 3 occurs in about 15 to 20% (ref.1). These data suggest that ankyrin-1 or band 3 defects may be common in HS. To test this we screened all 42 coding exons plus the 5' untranslated/promoter region of ankyrin-1 and the 19 coding exons of band 3 in 46 HS families. Twelve ankyrin-1 mutations and five band 3 mutations were identified. Missense mutations and a mutation in the putative ankyrin-1 promoter were common in recessive HS. In contrast, ankyrin-1 and band 3 frameshift and nonsense null mutations prevailed in dominant HS. Increased accumulation of the normal protein product partially compensated for the ankyrin-1 or band 3 defects in some of these null mutations. Our findings indicate that ankyrin-1 mutations are a major cause of dominant and recessive HS (approximately 35 to 65%), that band 3 mutations are less common (approximately 15 to 25%), and that the severity of HS is modified by factors other than the primary gene defect.
Ankyrins↗
Tenascin is an ubiquitous extracellular matrix protein of human renal interstitium in normal and pathologic conditions.
Tenascin, a large oligomeric glycoprotein, is a recent addition to a list of increasing extracellular matrix proteins. Previous studies have documented the strong expression of tenascin in embryonic kidney and in both normal and abnormal mature glomeruli implicating an important role of this extracellular matrix protein in nephrogenesis and glomerular scarring. Whether tenascin plays any role in interstitial fibrosis, a common final pathway of tubulointerstitial nephritis, is no known; on the other hand, a detailed knowledge of the structural components of interstitial fibrosis is essential for further studies on other fundamental aspects of this biologically and clinically important process. In this study, the expression of tenascin in the renal interstitium was immunohistochemically evaluated in 208 renal specimens during normal kidney (23 cases), acute tubular necrosis (8), acute tubulointerstitial nephritis (8), chronic primary tubulointerstitial nephritis (30), tubulointerstitial nephritis secondary to glomerular diseases of mild (46) and severe (55) degree, ischemic damage (24), and rejection (14). It was found that in normal kidney tenascin expression was limited to the medullary interstitium. In kidney with tubulointerstitial nephritis, tenascin was ubiquitously and constantly expressed in any areas with tubulointerstitial damage regardless of diagnosis, etiology, the cortical vs. medullary location of the lesions, stage of the fibrogenetic process, density of fibroblasts, or severity of interstitial inflammation in the affected areas. Indeed, strong tenascin expression was seen in areas where there was only interstitial edema or inflammation as judged by routine light microscopic preparations. In summary, this study systematically documents tenascin as a novel extracellular matrix protein selectively expressed in the medullary interstitium in normal kidney, and ubiquitously present in areas with interstitial fibrosis.
Antibody Specificity↗
Recognition of synthetic 104-mer and 102-mer peptides corresponding to N- and C-terminal nonrepeat regions of the Plasmodium falciparum circumsporozoite protein by sera from human donors.
In the present work, we analyze the recognition of synthetic polypeptides encompassing the aminoterminal (amino acids 22-125) and the carboxy terminal (289-390) regions of the circumsporozoite (CS) protein of Plasmodium falciparum by sera from donors living in endemic area of South America and Africa. Two populations were studied: one on the Colombian Pacific coast, with low endemicity for malaria; and a western African village exposed to a very intense transmission of P. falciparum. Antibodies directed to the two polypeptides were found at high titers in both populations. Furthermore, this response was observed in individuals lacking antibodies to the highly repetitive central sequence of the CS protein (NANP). The epitopes responsible for this recognition were mapped to the region 81-125 and 316-346 of the N- and C-termini, respectively. When the two populations were compared, both showed high titers of antibodies to the two flanking peptides. However, while 95% of the sera from African adults showed antibodies against the repeat region of the CS protein, only 37% of the Colombian adults studied had these antibodies. Furthermore, African donors of various ages exhibited different patterns of recognition of the two polypeptides. In African children less than five years of age, antibodies were found in comparable levels to Colombian adults; however, in older African donors, the response to NANP became dominant. These findings may reflect the skewing effect of the humoral response towards the central repetitive epitope under conditions of frequent exposure to malaria infections. The production of such polypeptides encompassing regions that contain multiple epitopes for antibodies, T helper, and cytotoxic T lymphocyte epitopes would be advantageous in the generation of new and more efficient malaria vaccines.
Adolescent↗
Renal abnormality of calcium handling in spontaneously hypertensive rats.
Hypercalciuria has been observed in human and experimental hypertension. The distal convoluted tubule (DCT) is the site of fine regulation for Ca2+ excretion. We assessed the cellular factors responsible for Ca2+ reabsorption in the DCT of spontaneously hypertensive rats (SHR). Vitamin D3 dependent Ca-binding protein 28k (CaBP28k), a factor involved in Ca2+ influx, and plasma membrane Ca ATPases (PMCA), a factor involved in Ca2+ efflux, were studied in hypertensive 16-week-old SHR and normotensive Wistar-Kyoto rats (WKY). mRNA levels for CaBP28k, PMCA 2 and PMCA 4 were not different in the two strains. However, CaBP28k protein was more abundant, and PMCA protein was less abundant in SHR than in WKY. PMCA antibody recognized only DCT in the two strains. In conclusion, decreased PMCA in DCT may be responsible for the hypercalciuria in SHR.
Animals↗
Cell calcium and arterial blood pressure.
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Animals↗
Plasma membrane and sarcoplasmic reticulum Ca-ATPase and smooth muscle.
Calcium ions (Ca2+) are involved in the regulation of many cellular activities. The Ca-ATPase(s) of the plasma membrane and of the endoplasmic reticulum play an important role in controlling the intracellular Ca2+ concentration. Therefore, it is not unexpected that these enzymes are modulated by different factors. The activity of the plasma membrane Ca-ATPase is modified by the amount of negatively charged phospholipids surrounding the enzyme. The regulation of the endoplasmic reticulum Ca-ATPase depends on the phosphorylation of phospholamban by cAMP- and cGMP-dependent protein kinase. These two different Ca2+ transport ATPases are present in both visceral and vascular smooth muscle, but tissue- and species-dependent differences in their relative amount have been observed. In this article we will review the characteristics of Ca-ATPases of the smooth muscle.
Animals↗
Cell calcium and arterial blood pressure.
In hypertensive humans and animals, intracellular calcium (Ca2+) has been found to be elevated in several cell types, including platelets, red blood cells, and smooth muscle cells. The messenger role of calcium requires its maintenance within cells at very low (submicromolar) ionic concentrations. This transcellular gradient is maintained by the reversible complexing of calcium to specific proteins. Intracellular free calcium can increase through an enhanced influx, release from intracellular stores, or a reduced efflux of calcium from the cell. Calcium channels are found to be increased in activity in some studies of hypertensive animals, but not in others. Sequestration of calcium within the cell has also been implicated in the increased cytosolic calcium in hypertension. Plasma membrane adenosine triphosphatases (ATPases) play a significant role in calcium extrusion; and the activity of these pumps has been found to be decreased in several human and animal studies. A single cause of the cellular calcium alterations in hypertension is not completely clear.
Animals↗
Differential expression of plasma membrane calcium pump mRNA isoforms in rat osteoblast-like cells.
This study was conducted to identify the plasma membrane Ca2+ transport ATPase (PMCA) mRNA isoforms expressed in rat osteoblast-like cells as PMCAs are likely to participate in calcium deposition in bone. We designed oligonucleotide primers for each PMCA isoform based on rat cDNA sequences in order to develop reverse transcription polymerase chain reaction (RT-PCR) assays. Rat kidney total RNA was used to validate the assays as we have shown that each isoform is present in kidney. When used in RT-PCR assays each primer pair gave rise to a single major product of the appropriate size. Southern blot analysis of the PCR products with oligonucleotide probes specific for each isoform revealed that each probe hybridized only to the expected product. Reamplification of purified PCR products with probe and antisense primers gave rise to products of appropriate size, further confirming the identity of the products. Using these primers we have identified the presence of transcripts for PMCA1, 2 and 4 in RNA from UMR-106 osteoblasts and PMCA1 in RNA from ROS 17/2.8 osteoblasts. We conclude that the two major rat cell lines used as models to study osteoblast function differentially express PMCA mRNA isoforms.
Animals↗