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Biomedical subjects

A M Gonzalez

Publications and source records attributed to A M Gonzalez.

At least 73 records · Page 4Linked to original sources
PubMed1991

Neutrophil aldose reductase activity and its association with established diabetic microvascular complications.

Direct investigation of the polyol pathway is rarely possible in studies of human diabetes. A spectrophotometric assay has been developed for the measurement of aldose reductase and sorbitol dehydrogenase activity in the neutrophil. Neutrophil aldose reductase activity was increased in patients with Type 1 diabetes with complications (median 40 (interquartile range 28-48) u, where 1 unit of enzyme activity = nmol NADPH min-1 10(8)-cells-1) compared with those without complications (20 (16-36) u, p less than 0.01) and normal control subjects (20 (8-36) u, p less than 0.01). In Type 2 diabetes, patients with complications also had higher aldose reductase activity (40 (28-52) u) than those without complications (24 (16-36) u, p less than 0.01). There were no differences between patients without complications and normal control subjects. Sorbitol dehydrogenase activity was decreased in diabetic patients (p less than 0.02) but not significantly different between diabetic patients with and without complications.

Aldehyde Reductase↗
PubMed1991

Expression of basic fibroblast growth factor and its receptor in the rat subfornical organ.

Basic fibroblast growth factor (FGF), its mRNA and the mRNA that encodes for its receptor have all been localized in the rat subfornical organ (SFO). Basic FGF is widely distributed throughout the SFO; it is present in neurons, in the vascular basement membrane of lateral blood vessels (but not those within the SFO) and in ependymal cells surrounding the SFO. Results of in situ hybridization show that the expression of basic FGF mRNA is detected throughout the organ. Similarly, the expression of flg, the gene for the putative basic FGF receptor, can also be detected in the SFO. The results all support the possibility that this growth factor may modulate the known physiological functions of the SFO.

Animals↗
PubMed1991

Vascular response to basic fibroblast growth factor when infused onto the normal adventitia or into the injured media of the rat carotid artery.

Immunohistochemical techniques localize basic fibroblast growth factor (FGF) in endothelial and smooth muscle cells of the common carotid artery. Thus, we studied the effect in rats of basic FGF infused for 14 days onto the adventitia or into the media in vivo. In untreated rats, the adventitial layer is uniform, and few vessels are observed in cross sections (mean +/- SEM is 0.351 +/- 0.16 capillaries/field at a magnification of x 480). Whereas saline infusion increases the mean number of vasa vasorum to 2.73 +/- 0.011 capillaries/field (p less than 0.01), basic FGF (1 ng/microliter/hr) increases the capillary number to 13.4 +/- 0.67 capillaries/field. The effects are local and restricted to the site of delivery; no cell proliferation is observed even 2 mm from the site of infusion. There is also no evidence of the infiltration of macrophages and monocytes. In an effort to determine the effect of basic FGF in the media, a small longitudinal (1-mm) incision was made in the adventitia, and saline or basic FGF (1 ng/microliter/hr) was infused for 14 days into the arterial wall. Under these conditions, basic FGF is a potent inducer of smooth muscle cell proliferation in the vascular wall as well as of new capillaries. In these instances, however, the capillaries formed are thick-walled. The results support the hypothesis that basic FGF may be contributing to the growth and maintenance of the vasa vasorum and of vascular smooth muscle cells.

Animals↗
PubMed1991

Independent expression of the alpha and beta c-erbA genes in developing rat brain.

Thyroid hormone is important for normal brain development. Cellular responses to thyroid hormone are mediated by multiple nuclear receptors, classified into alpha- and beta-subtypes. In the rat, expression of both the alpha and beta genes results in several translation products. By using cRNA probes common to alpha transcripts or specific for alpha-1 and beta-1, we have studied the distribution of these transcripts in rat brain at different stages of development from embryonic day 14 to adult age by using in situ hybridization histochemistry. On embryonic day 14, the alpha-1 mRNA is already widely expressed at a low level in the developing brain. The alpha-1 mRNA is developmentally regulated and showed a peak in expression during the first 3 postnatal weeks in the cerebral cortex, amygdala, hippocampus, and cerebellum. The probe common to the alpha transcripts detected a widespread distribution and high levels of these forms in the same regions throughout postnatal development. The level of beta-1 mRNA before birth was low or undetectable. The beta-1 transcript showed developmental regulation as well, with a high level at birth in the mitral cell layer of the olfactory bulb, accumbens nucleus, caudate, and hippocampal field CA1 and increasing levels in other regions later during development. Complementary expression of the alpha and beta forms was seen in the cerebral cortex and hippocampus. The differential temporal and spatial distribution as well as coexpression at comparable levels in certain brain regions suggest different roles for the c-erbA proteins during brain development and in the mature animal.

Age Factors↗
PubMed1991

Multiple forms of bFGF: differential nuclear and cell surface localization.

The single copy gene for human basic fibroblast growth factor (bFGF) has been shown to encode not one but multiple proteins of 24, 23, 22 and 18 kD. Although bioactivities of the 18 kD protein are currently used to define bFGF gene function, it is not yet known if the three larger proteins have these same bioactivities or whether they will serve to define new bFGF gene functions. In this report we present a comparative study describing the de novo synthesis, transport, processing and intracellular location of individual bFGF isoforms. Data from cDNA mutagenesis and COS cell expression experiments show that individual isoforms are differentially localized to either the cell surface or to the nucleus. The 24, 23 and 22 kD proteins (CUG-mediated initiation) exclusively localize in the nucleus while the 18 kD protein (AUG-mediated initiation) is preferentially exported onto the cell surface, but is not released into the surrounding culture medium. Specific CUG or AUG translation initiation codons are necessary and sufficient for the synthesis of each isoform examined and thereby, indirectly, mediate differential localization. Since bFGF does not contain the characteristic signals predicted for cell surface or nuclear targeting, our continuing studies will either unmask its functionally equivalent domain(s) or will identify the requisite participation of yet unknown cellular components.

Animals↗
PubMed1991

The role of aldose reductase inhibition in diabetic neutrophil phagocytosis and killing.

This study examines whether an aldose reductase inhibitor (statil, ICI) can enhance neutrophil oxidative killing by diabetic neutrophils. We have examined a radiometric assay of phagocytosis and killing of Candida albicans by neutrophils from 20 controls and 20 subjects with insulin-dependent diabetes under various in vitro glucose concentrations. Glucose was present at 5, 10 and 20 mM in the presence and absence of statil (11 microM). Phagocytosis was unaffected by raised glucose levels in controls and in diabetic subjects. Killing by the diabetic cells was inhibited by increasing concentrations of glucose, killing was 18.9 +/- 2.0, 16.9 +/- 2.4 and 14.8 +/- 2.0% (mean +/- s.e.m.) at 5, 10 and 20 mM glucose, respectively (P less than 0.05). With the addition of statil under the same conditions killing improved to 19.3 +/- 2.0, 23.2 +/- 2.2 and 23.6 +/- 2.4 (P less than 0.01), these values were similar to the controls (P greater than 0.01). We conclude therefore that aldose reductase inhibition restores oxidative killing to normal.

Adult↗
PubMed1990

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↗
PubMed1990

Distribution of basic fibroblast growth factor in the 18-day rat fetus: localization in the basement membranes of diverse tissues.

Immunohistochemical methods were used to study the distribution of basic FGF in the 18-d rat fetus. The results reveal a pattern of widespread yet specific staining that is consistent with the wide distribution of basic FGF. Immunoreactive basic FGF is associated with mesenchymal structures, mesoderm- and neuroectoderm-derived cells, and their extracellular matrices. As an example, skeletal and smooth muscle cells are strongly positive. The basement membrane underlying the epithelia always contain basic FGF. In some tissues (i.e., cartilage and bone) the intensity of immunostaining is dependent on the stage of cell differentiation. Although the staining of tissues is primarily associated with the extracellular matrix, there is significant intracellular staining in various cell types. This is particularly evident in the endocrine cells of the adrenal cortex, testis, and ovary. The histochemical findings reported here support the notion that basic FGF has the characteristics required to mediate many of the effects of the mesenchyme on cell growth and differentiation. The significance of these findings in understanding the role of basic FGF in regulating cell proliferation and differentiation is discussed.

Animals↗
PubMed1989

Comparative study of pentoxifylline vs antiaggregants in patients with transient ischaemic attacks.

Out of 235 patients with recent cerebral transient ischaemic attacks, 208 subjects were available for final evaluation after 6 months' randomised treatment with either pentoxifylline (PTX 1200 mg/day) or a combination (ASAD) of acetylsalicylic acid (ASA, 1050 mg/day) and dipyridamole (D, 150 mg/day). Prevention of TIA, stroke or death attributable to previous events were endpoint criteria. The pentoxifylline group (n = 100) exhibited no recurrent episodes in 86 patients (86%). TIA occurred in 9 patients, stroke in 5 patients and there was 1 death. In the ASAD group (n = 108) no recurrence of ischaemic episodes was recorded in 82 cases (75.9%). TIA occurred in 20 patients, stroke in 6 patients and there were 3 deaths of vascular origin. Side effects were recorded in 4 ASAD and 1 PTX patients. The total rate of recurrence was 14% with PTX as compared to 24.1% with ASAD treatment.

Aged↗
PubMed1989

Basic fibroblast growth factor (FGF) in the central nervous system: identification of specific loci of basic FGF expression in the rat brain.

The expression of basic FGF mRNA, while virtually absent in peripheral tissues, appears to be constitutively expressed in the central nervous system. As such, while it is difficult to detect any mRNA encoding basic FGF in the heart, lung, kidneys, ovaries, liver, or pituitary of rats, the levels are easily detected in brain. A regional analysis of the expression of basic FGF mRNA in brain reveals that it is widely distributed in the cortex (frontal, parietal, and occipital), the hippocampus, hypothalamus, and pons. Only a few loci of basic FGF synthesis are detected by in situ hybridization and include layers 2 and 6 of the medial (cingulate) cortex, the indusium griseum, fasciola cinereum, and field CA2 of the hippocampus. The identification of specific cell populations in the brain, and particularly in the hippocampus, that synthesize basic FGF supports the notion that this potent neurotrophic factor is involved in normal CNS function and that the presence (or absence) of its expression may be linked to the pathogenesis of the neurogenerative diseases characterizing these various loci. The significance of these findings with respect to the regulation of basic FGF expression in peripheral tissue and the central nervous system is discussed.

Animals↗