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Biomedical subjects

J Alvarez

Publications and source records attributed to J Alvarez.

At least 253 records · Page 14Linked to original sources

Basic fibroblast growth factor in Alzheimer's disease.

We have examined the presence of basic fibroblast growth factor (FGF) in normal and in Alzheimer brains, studied the distribution of the mitogen by immunohistochemical techniques, measured the quantities of growth factor in selected areas of the brain (Brodmann areas 10/11 and 20/21), characterized the molecular forms by Western blotting and determined its sites of synthesis by in situ hybridization. Although the same molecular forms of basic FGF are found in control and Alzheimer brains, basic FGF is increased in the brains of Alzheimer's patients. Furthermore, basic FGF is not distributed in an identical fashion to normal and Alzheimer brains, but is found in association with the lesions that characterize this disease. In normal controls (n = 5), basic FGF was found to be widely distributed throughout the three brain regions examined (prefrontal cortex, hippocampus, and hypothalamus). Immunoreactivity was observed within astrocytes in both the grey and white matter, as well as within neuronal perikarya. Brain tissues that were obtained from Alzheimer patients (N = 4) showed a substantial increase in the overall specific staining of astrocytes and neurons, particularly in areas of reactive gliosis. Focal concentration of immunoreactive basic FGF was evident within the neuritic plaques, and could be clearly seen in association with the neurofibrillary tangles present within neuronal perikarya. The possibility that basic FGF expression in the CNS is linked to the pathogenesis of the disease is discussed.

Alzheimer Disease↗

Calibers and microtubules of nerve fibers: differential effect of undernutrition in developing and adult rats.

Sural nerves of 9-week-old rats undernourished since birth, and of adult rats food-restricted for 27 and 48 days, were studied to explore the effect of severe undernutrition on the caliber and microtubules of axons in growing and non-growing animals. In 9-week-old undernourished rats, the number and caliber of myelinated fibers were normal while the cross-sectional area of non-medullated fibers was 29% smaller than controls. By contrast, in adult undernourished rats the cross-sectional area of myelinated fibers was affected sooner and to a greater extent (-28%) than that of non-medullated fibers (-23%). Regardless of age, in both controls and in undernourished rats non-medullated fibers of equal caliber had similar microtubular content. The same was found in 3-microns myelinated axons. These findings indicate that food restriction affects proportionately caliber and microtubules of axons. It is proposed that the anatomy of the axon is in a dynamic equilibrium and that microtubules participate in the specification of the axonal caliber.

Age Factors↗

Osteoclast cytosolic calcium, regulated by voltage-gated calcium channels and extracellular calcium, controls podosome assembly and bone resorption.

The mechanisms of Ca2+ entry and their effects on cell function were investigated in cultured chicken osteoclasts and putative osteoclasts produced by fusion of mononuclear cell precursors. Voltage-gated Ca2+ channels (VGCC) were detected by the effects of membrane depolarization with K+, BAY K 8644, and dihydropyridine antagonists. K+ produced dose-dependent increases of cytosolic calcium ([Ca2+]i) in osteoclasts on glass coverslips. Half-maximal effects were achieved at 70 mM K+. The effects of K+ were completely inhibited by dihydropyridine derivative Ca2+ channel blocking agents. BAY K 8644 (5 X 10(-6) M), a VGCC agonist, stimulated Ca2+ entry which was inhibited by nicardipine. VGCCs were inactivated by the attachment of osteoclasts to bone, indicating a rapid phenotypic change in Ca2+ entry mechanisms associated with adhesion of osteoclasts to their resorption substrate. Increasing extracellular Ca2+ ([Ca2+]e) induced Ca2+ release from intracellular stores and Ca2+ influx. The Ca2+ release was blocked by dantrolene (10(-5) M), and the influx by La3+. The effects of [Ca2+]e on [Ca2+]i suggests the presence of a Ca2+ receptor on the osteoclast cell membrane that could be coupled to mechanisms regulating cell function. Expression of the [Ca2+]e effect on [Ca2+]i was similar in the presence or absence of bone matrix substrate. Each of the mechanisms producing increases in [Ca2+]i, (membrane depolarization, BAY K 8644, and [Ca2+]e) reduced expression of the osteoclast-specific adhesion structure, the podosome. The decrease in podosome expression was mirrored by a 50% decrease in bone resorptive activity. Thus, stimulated increases of osteoclast [Ca2+]i lead to cytoskeletal changes affecting cell adhesion and decreasing bone resorptive activity.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Ischemic stroke in young adults. II. Analysis of risk factors in the etiological subgroups.

A prospective study on 386 consecutive patients affected of ischemic stroke (IS) has been analysed in relation to etiologies, comparing them with a control group of 100 people. The atherotrombotic etiology subgroups are associated with family history of stroke, risk factors, atheromatosis, occlusive peripheral arteriopathy, previous of stroke, high levels of hematocrit and hemoglobin, impaired lipid fractions and high levels of uric acid. The cardiac embolism etiology subgroups are associated with the presence of personal history of stroke, just as the mitral valva prolapse (MVP) patients group. The migraine group is significantly related with the intake of oral contraceptives.

Adult↗

Microtubular packing varies along the course of motor and sensory axons: possible regulation of microtubules by environmental cues.

In the toad Xenopus laevis, the microtubular density of 3-microns myelinated fibres was assessed in peripheral nerves, dorsal and ventral roots, and dorsal and ventral funiculi of the spinal cord. In the roots, the axonal microtubular density was 6 microtubules/microns 2 and twice as much at the other sampling sites. This indicates that the pattern of the microtubular packing may vary along the course of the axon. We propose that axonal microtubules are regulated by local cues.

Animals↗

Intracellular Ca2+ potentiates Na+/H+ exchange and cell differentiation induced by phorbol ester in U937 cells.

The human cell line U937 differentiates to monocyte macrophage-like cells in response to tumour-promoting phorbol esters. This effect is attributed to activation of protein kinase C. We show here that U937 cell differentiation induced by 12-O-tetradecanoylphorbol 13-acetate (TPA) is associated with cytoplasmic alkalinization. Ethyl-isopropyl-amiloride (EIPA), a potent inhibitor of Na+/H+ exchange, blocked both cytoplasmic alkalinization and cell differentiation. Cell acidification by addition of 2-4 mM sodium propionate also blocked TPA-induced U937 cell differentiation. These results suggest that a sustained cell alkalinization mediated by activation of Na+/H+ exchange is essential for TPA-induced differentiation in U937 cells. The increase of cytoplasmic free calcium concentration ([Ca2+]i) by addition of the calcium ionophore ionomycin enhanced TPA-induced alkalinization by increasing the apparent affinity of the Na+/H+ antiporter for intracellular H+. Treatment with ionomycin also potentiated differentiation of U937 cells induced by TPA. This synergism suggests that [Ca2+]i either potentiates the activation of protein kinase C or triggers additional transducing mechanisms. The key events of this interaction occur during the first 30 min of treatment, even though cell differentiation manifests much later.

Amiloride↗

On the asymmetry of the primary branching of vagal sensory axons: possible role of the supporting tissue.

Central and peripheral nonmedullated processes of vagal nodosal neurons of the cat were studied in normal nerves and after regeneration along their anatomical course and along the hypoglossal nerve. Nonmedullated fibers above the ganglion and in the root had comparable sizes (approximately 0.37 micron2) and caliber distribution. Below the ganglion, the cross-sectional area increased to 1.0 micron2. In axons of equal caliber, supranodosal and radicular fibers had similar microtubular densities while infranodosal fibers had two- to threefold that of the former. Regenerated fibers were studied after a recovery period of 6-9 months. Regrown axons were smaller than their parent axons; in turn, these were smaller than normal axons. This holds for central and peripheral nodosal branches, for homologous and heterologous regeneration. Regrown peripheral branches, either along their anatomical pathway or along the hypoglossal nerve, showed no change in microtubular density. Central branches exhibited their characteristic microtubular content when they regenerated along their anatomical course, but when regrowth took place along the hypoglossal nerve, the original low microtubular content of these branches increased to match the high content of peripheral fibers; parent central axons also shifted their microtubular content toward the pattern of peripheral fibers. We propose that the supporting tissue participates in specifying the organization of axonal microtubules.

Animals↗

Inhibition of red cell Ca2+-dependent K+ channels by snake venoms.

We have investigated the effects of several snake venoms on the Ca2+-dependent K+ channels of human red cells. A heat-resistant component of the venom of the snake Notechis scutatus irreversibly inhibited Ca2+-dependent K+ transport with a Ki value of 0.1-0.2 micrograms/ml. Metabolic changes of the cells modified the maximal effect of the venom. Binding of the venom required extracellular Ca2+ and was quick, but development of full inhibition required additional time. The effects of the venoms from Notechis scutatus and Leiurus quinquestriatus were additive, suggesting that both venoms act through different mechanisms. Venoms of the snakes Vipera russelli russelli and Oxyuranus scutellatus also inhibited Ca2+-dependent K+ transport with the same characteristics as the Notechis scutatus venom.

Biological Transport↗

Is the supply of axoplasmic proteins a burden for the cell body? Morphometry of sensory neurons and amino acid incorporation into their cell bodies.

Since the perikaryon is considered to be the source of all axoplasmic proteins, we estimated the amount of protein synthesized in cell bodies and axoplasmic volumes of sensory neurons of two anuran species (Xenopus and Caudiverbera) to detect a correlation between these variables. The range of cell body volumes was 1:28 and 1:38 in Xenopus and Caudiverbera, respectively, while that of axoplasmic volumes was 1:5000-6000. The protein synthesis in glial and neuronal cell bodies was assessed with pulses of labeled amino acids followed by radioautography. No obvious correlation was found between axoplasmic volume and either rate or amount of amino acid incorporated into cell bodies. The rate of amino acid incorporation into glial and neuronal cell bodies was of the same order of magnitude. Results suggest that the maintenance of the axoplasm does not seem to be a burden for the perikaryon.

Amino Acids↗

Risk factors for acute pancreatitis in patients with migrating gallstones.

Stool screening for gallstones and ultrasound monitoring of diameter changes of the biliary and pancreatic duct were performed in 129 patients with choledocholithiasis. Gallstone migration was found in 44 patients, all of whom were operated on electively. At surgery, acute pancreatic lesions were found in 16 patients; in the remaining 28 there was no evidence of pancreatic inflammation. There were no significant differences among patients in both groups regarding sex, age, stone size, shape or number found in stools, interval between admission and migration, or the presence of a dilated pancreatic duct before migration. Pancreatic duct reflux, however, was significantly more frequent in cholangiograms of patients with acute pancreatitis, implying that a common channel may be a major factor relating to acute pancreatitis in patients with migrating gallstones.

Acute Disease↗

Anti-200 kDa neurofilament antibody cross-reacts with microtubule-associated protein-2 (MAP-2).

An antibody prepared against purified 200-kDa neurofilament (NF) subunit was found to cross-react with a high molecular weight polypeptide present in rat brain cytoskeletal extracts starting from early postnatal development. This polypeptide was found to be highly concentrated in microtubule preparations and was specifically recognized as the 280-kDa microtubule-associated protein-2 (MAP-2). Our results, besides suggesting the existence of common epitopes between the heavy NF subunit and MAP-2, suggest the possibility of an interaction between two of the most important neuronal cytoskeletal organelles: NFs and microtubules.

Animals↗

Sinus node function and protamine sulfate.

This report analyzes the effects of protamine sulfate (PS) on the heart rate and sinoatrial node function in dogs anesthetized with diazepam, fentanyl, and pancuronium bromide, and subjected to different modalities of extracorporeal circulation (ECC). All groups were given 3 mg/kg of heparin sodium and 5 mg/kg of PS. The sinus node function was evaluated by means of sinoatrial conduction time (SACT), absolute sinus node recovery time (SNRTa), and corrected sinus node recovery time (SNRTc). The spontaneous heart rate (HR) of the animals was also analyzed. Under the experimental conditions established in this study, the intravenous administration of a bolus of PS produced a decrease in the HR in all the groups, regardless of the type of ECC used. The modifications in the conduction and recovery times of the sinus node by PS did not correlate with those of the heart rate; the sinoatrial conduction time increased in groups subjected to ECC, while the absolute and corrected recovery times of the sinus node were prolonged only in the group that underwent rapid rewarming.

Animals↗

Ischemic stroke in young adults. I. Analysis of the etiological subgroups.

An ischemic stroke (IS) group including 386 patients under 50 years old is analysed taking into account different etiological subgroups and comparing risk factors against a control group of 100 people. The series points out the presence of 66.1% patients included in the inconclusive-atherothrombosis group, of which 22.7% had defined criteria of atheromatosis, while 11.6% were diagnosed of lacunar infarct. 13.5% of cases were considered as cardiac origin embolisms, and 14.1% were affected of mitral valve prolapse. The migraine group includes 4.9% of the patients while 17.6% belong to the miscellaneous group. The comparison of each of these groups with the control group showed significant differences for family history of stroke, personal history of peripheral arteriopathy, tobacco, arterial hypertension and previous IS.

Adolescent↗