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Biomedical subjects

G A Lopez

Publications and source records attributed to G A Lopez.

At least 19 recordsLinked to original sources
PubMed2000

Update on therapies for acute ischemic stroke.

Acute ischemic stroke is now considered a neurological emergency for which there are new therapies. Neurosurgeons and neurologists need to remain apprised of advances in this field. The authors discuss approved and emerging therapies for patients suffering from acute ischemic stroke, based on a review of recent publications. Currently, intravenous tissue-type plasminogen activator is the only Food and Drug Administration-approved therapy for acute ischemic stroke. Intraarterial delivery of thrombolytics is a promising treatment and may be effective in selected patients. Other therapies for acute cerebral ischemia are intriguing but still in the investigational stages.

Docosahexaenoic Acids↗
PubMed2000

F1 hybrid inviability in eucalyptus: the case of E. ovata x E. globulus.

The impact of inbreeding and hybridization on fitness was compared in the two co-occurring forest tree species, Eucalyptus ovata and E. globulus, aimed at explaining the rarity of their hybrids in nature. The success of selfing, open-pollination and outcrossing of both species and interspecific hybridization was monitored from seed-set to 10-year's growth in a field trial. There was a unilateral barrier to hybridization with seed-set obtained only with E. ovata females. The F1 hybrids exhibited reduced viability compared to intraspecific cross-types at virtually all stages of the life cycle and are clearly at a selective disadvantage compared with their open-pollinated E. ovata half-sibs with which they would directly compete in nature. Eucalyptus ovata and E. globulus overlap in their flowering time but the F1 hybrids flowered later with virtually no overlap with either species. The asynchronous flowering and reduced reproductive fitness of F1 hybrids would markedly limit the opportunity for advanced generation hybridization. Inbreeding similarly had a deleterious effect on the fitness of both species, and the F1 hybrids were most competitive with the E. ovata selfs. It is argued that changes in inbreeding levels of parental populations may be a key factor affecting the relative fitness of hybrids and their potential to impact on the pure species gene pool. Reduced fitness of the pure species through inbreeding may result in hybridization having its greatest evolutionary impact in small founder or relict populations.

Biological Evolution↗
PubMed1995

Changes in various plasma lipid components, glucose, and insulin in Spermophilus lateralis during hibernation.

This study evaluated fat mobilization as related to gluconeogenesis in two age groups of hibernating golden-mantled ground squirrels (Spermophilus lateralis). Our experimental group consisted of a total of 16 male and 15 female squirrels. Plasma samples were collected from selected animals being killed weekly from January to March, and the concentration of triglycerides, glycerol (GY), free fatty acids (FFA), total cholesterol, lipase activity, glucose, and insulin, were determined by biochemical assays and radioimmunoassay. Our results showed a mean FFA/GY ratio of five, which was higher than the predicted value of three, suggesting a significant depletion of GY and an enhanced rate of gluconeogenesis via GY to maintain glucose homeostasis in the hibernating animals. The factor of age did not significantly affect plasma lipid components. However, in the male group, plasma glucose levels were significantly higher for adults than for juveniles. Overall, females had significantly higher plasma glucose levels than males (150 +/- 11 vs. 110 +/- 8 mg%, P < 0.05). In the adult group, a gender influence was also seen on plasma insulin levels, with females' being higher than males' (66 +/- 13 vs. 25 +/- 3 microIU/ml, P < 0.01). We suggest that during hibernation, female squirrels may have a higher rate of lipolysis and gluconeogenesis along with a lower glucose utilization than their male counterparts. Additionally, adult females may exhibit a higher peripheral insulin resistance during hibernation than adult males, a possibility which merits further study.

Age Factors↗
PubMed1994

Evidence that the S6 segment of the Shaker voltage-gated K+ channel comprises part of the pore.

Potassium channels are highly selective and allow the rapid flux of potassium ions through their pore. Several studies have implicated the H5 (P or SS1-SS2) segment as part of the pore in voltage-gated ion channels. The proposal that H5 spans at least 80% of the electric potential drop across the K+ channel pore is based on altered internal tetraethylammonium sensitivity arising from mutations of H5 residues that are 100% conserved among K+ channels having differing sensitivity to tetraethylammonium. Here we report that the S6 segment is also involved in K+ ion permeation and in governing the sensitivity to internal tetraethylammonium and barium. Transplanting the S6 segment of NGK2 into Shaker causes this S6 chimaera to adopt the single-channel conductance and sensitivity to internal tetraethylammonium and barium ions from the NGK2 channel. The differences between NGK2 and Shaker in external tetraethylammonium sensitivity, but not single-channel conductance, can be attributed to the differences in their H5 sequences. Three nonconserved S6 residues have been found to affect either single-channel conductance or internal tetraethylammonium sensitivity.

Amino Acid Sequence↗
PubMed1992

Plasma lipoprotein cholesterol concentrations in the golden-mantled ground squirrel (Spermophilus lateralis): a comparison between pre-hibernators and hibernators.

1. The concentrations of total cholesterol (free cholesterol plus cholesteryl ester) in the plasma and in two lipoprotein fractions of golden-mantled ground squirrels (Spermophilus lateralis) were measured during pre-hibernation and compared to those values measured during hibernation. 2. Hibernating ground squirrels had significantly higher (P less than 0.005) very low density lipoprotein plus low density lipoprotein cholesterol (VLDL + LDL-C) concentrations than did pre-hibernating ground squirrels. 3. Hibernating squirrels additionally exhibited significantly higher (P less than 0.005) total plasma cholesterol concentration per high density lipoprotein cholesterol concentration (TPC/HDL-C) ratios than did pre-hibernating squirrels. 4. The significant differences in the lipoprotein cholesterol concentrations observed in this study suggest that lipoprotein metabolism in pre-hibernators was significantly different from that in hibernators and was a reflection of the marked biochemical and physiological adjustments these animals must undergo during their transition from pre-hibernation to hibernation.

Animals↗
PubMed1992

Gender influences the in vitro renin release responses to dopamine and adrenergic receptor blockade in the summer-active ground squirrel Spermophilus lateralis.

1. 10(-4) M Dopamine stimulated and 10(-7) M inhibited in vitro resting renin release (RR) only in the female animals. 2. Alpha- or beta-adrenergic blockade prevented the stimulation but not the inhibition of RR by dopamine in the female animals. 3. Membrane receptor mechanisms mediating these changes do not involve alterations in tissue cyclic AMP content. 4. The sensitivity of the juxtaglomerular cells to dopamine challenge is gender dependent during summer activity.

Adrenergic Antagonists↗
PubMed1991

beta-NGF-endopeptidase: structure and activity of a kallikrein encoded by the gene mGK-22.

Mouse nerve growth factor (NGF) is cleaved at a histidine-methionine bond to release an NH2-terminal octapeptide (NGF1-8). The enzyme responsible, beta-NGF-endopeptidase, is structurally and functionally similar to gamma-NGF and epidermal growth factor-binding protein (EGF-BP) and cleaves mouse low molecular weight kininogen to produce bradykinin-like activity. These data have suggested that, like gamma-NGF and EGF-BP, beta-NGF-endopeptidase is a mouse glandular kallikrein. Evidence for a physiological role for NGF1-8 encouraged studies to further characterize the structure and function of this enzyme. Purified beta-NGF-endopeptidase migrated as a single band on isoelectric focusing and reducing SDS-polyacrylamide gels. As was expected, it removed NGF1-8 from NGF. Interestingly, enzymatic activity on an artificial substrate, and on NGF, was inhibited by NGF1-8 and by bradykinin. These studies further supported the view that beta-NGF-endopeptidase acts on both NGF and kininogen. The first 30 NH2-terminal amino acids of beta-NGF-endopeptidase were sequenced. This analysis demonstrated that the enzyme is encoded by the gene designated mGK-22 (Evans et al., 1987). The sequence of this gene corresponds to that of EGF-BP type A (Anundi et al., 1982; Drinkwater et al., 1987), and so studies were performed to determine whether or not beta-NGF-endopeptidase participates in EGF complex formation. Chromatographic and kinetic data gave no evidence that beta-NGF-endopeptidase is an EGF-binding protein. Our studies suggest that contamination of high molecular weight (HMW) EGF preparations with beta-NGF-endopeptidase erroneously led to earlier designation of the product of mGK-22 as an EGF-BP.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1991

Circulating lipoprotein cholesterol concentrations in the summer-active ground squirrel (Spermophilus lateralis): a comparison with those in humans and rabbits.

1. The concentrations of total cholesterol (free cholesterol plus cholesteryl ester) in the sera and in two lipoprotein fractions of golden-mantled ground squirrels (Spermophilus lateralis) were measured and compared to those found in humans and New Zealand White rabbits (Oryctolagus cuniculus). 2. Squirrels showed significantly higher concentrations of total serum cholesterol (TSC; P less than 0.0005), high density lipoprotein cholesterol (HDL-C; P less than 0.0005), and very low density plus low density lipoprotein cholesterol (VLDL + LDL-C; P less than 0.0005) than those in rabbits. 3. Squirrels had significantly higher TSC (P less than 0.0005) and HDL-C (P less than 0.0005) concentrations than did humans. 4. Squirrels additionally exhibited significantly lower TSC/HDL-C ratios than did rabbits (P less than 0.005) or humans (P less than 0.0005). 5. The significant differences in lipoprotein metabolism observed in this study between the active hibernator and non-hibernators, may reflect the marked biochemical and physiological adjustments hibernating species make throughout their circannual cycle.

Animals↗
PubMed1991

Hydrophobic substitution mutations in the S4 sequence alter voltage-dependent gating in Shaker K+ channels.

Voltage-activated Na+, Ca2+, and K+ channels contain a common motif, the S4 sequence, characterized by a basic residue at every third position interspersed mainly with hydrophobic residues. The S4 sequence is proposed to function as the voltage sensor and to move in response to membrane depolarization, triggering conformational changes that open the channel. This hypothesis has been tested in previous studies which revealed that mutations of the S4 basic residues often shift the curve of voltage dependence of activation along the voltage axis. We find that comparable or larger shifts are caused by conservative substitutions of hydrophobic residues in the S4 sequence of the Shaker K+ channel. We suggest that the S4 structure plays an essential role in determining the relative stabilities of the closed and open states of the channel.

Amino Acid Sequence↗
PubMed1991

Characterization of a mammalian cDNA for an inactivating voltage-sensitive K+ channel.

A cDNA clone encoding a K+ channel polypeptide with 72% amino acid sequence identity to Drosophila Shal was isolated from rat hippocampus. Functional expression of the cDNA in Xenopus oocytes generated 4-amino-pyridine-sensitive K+ channels displaying rapid inactivation kinetics. The fastest component of inactivation was slowed by the deletion of 3 basic residues in the amino-terminal region. Northern blots revealed that the mRNA encoding this K+ channel polypeptide was expressed at a similar level in the brain and in the heart. In situ hybridization revealed that the mRNA encoding this K+ channel appeared concentrated in the hippocampus, dentate gyrus, and habenular nucleus in the brain. Thus, this K+ channel polypeptide is likely to form some of the A-type K+ channels expressed in the mammalian nervous system and heart.

Amino Acid Sequence↗
PubMed1990

Changes in renal morphology and renin secretion in the golden-mantled ground squirrel (Spermophilus lateralis) during activity and hibernation.

Chronological changes in renal glomerular morphology and plasma renin activity were investigated during active and hibernating periods in the golden-mantled ground squirrel Spermophilus lateralis. The objective of this study was to determine whether the glomerular endothelium, visceral epithelium (podocytes), basement membrane, mesangial cells, proximal convoluted tubule cells and plasma renin activity exhibit measurable sequential differences between as well as within active and hibernating states at various time points. Limitations in the size of the experimental population prevented an evaluation of changes in these parameters during other important periods such as periodic arousal between hibernation bouts. In this study, glomerular endothelial pore number and epithelial filtration slit number significantly decreased by early hibernation when compared to those during summer activity, and then they increased back toward summer levels by late hibernation. In contrast, podocytic pedicel width along the glomerular basement membrane increased from summer activity to early hibernation, before significantly decreasing again by late hibernation. Mesangial cell and proximal convoluted tubule cell activity appeared increased during hibernation as compared to summer activity, whereas the width of the glomerular basement membrane showed no significant alterations throughout. Plasma renin activity significantly increased during early hibernation and mid-hibernation when compared to summer levels but had decreased by late hibernation toward summer values. The glomerular and plasma renin activity changes observed in this study clearly illustrate the drastic structural and functional adjustments which hibernating species make during torpor and also correlate well with the reported decrease in renal perfusion pressure and urine formation during hibernation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Renin release responses to in vitro prostaglandin challenge in the summer-active ground squirrel, Spermophilus lateralis.

1. Using a renal cortical slice preparation from the summer-active ground squirrel, Spermophilus lateralis, resting renin release (RR) and tissue cyclic AMP content (TcAMPC) levels were found to be significantly higher and lower, respectively, than those previously reported for its hibernating counterpart. 2. At a 10(-5) M dose, PGE2 but not PGE1, PGF2-alpha or PGA1, significantly stimulated RR in the summer-active ground squirrel (SAGS). 3. Addition of agents which normally increase TcAMPC significantly potentiated the effect of PGE1, while preventing that of PGE2, on RR and TcAMPC. 4. Opposite TcAMPC changes may mediate the in vitro RR responses to PGE1 and PGE2 administration in the SAGS.

Alprostadil↗
PubMed1986

Prostaglandin E1 (PGE1) stimulates in vitro renin release in the hibernating ground squirrel.

Using a renal cortical slice preparation obtained from hibernating ground squirrels, this study investigated whether three major intrarenal prostaglandins (PG) and other agents added at a 10(-5) M dose can affect renin release (RR), and if their effect on RR is correlated with changes in tissue cyclic AMP content (tcAMPc). Resting in vitro levels for RR and tcAMPc during hibernation were found to be comparable to those observed in non-hibernating (NH) mammals. Addition of PGE1 significantly stimulated RR while PGE2 and PGF2-alpha were ineffective. None of the three PG's tested altered resting levels of tcAMPC. When added by itself or in conjunction with any of the three PG's, the phosphodiesterase inhibitor theophylline did not modify resting levels of RR and tcAMPc, but it prevented the previous stimulatory effect of PGE1 alone on RR. Addition of lipid-soluble dcAMP, either alone or in conjunction with any of the three PG's, resulted in an increase in tcAMPc in all instances, no change in resting RR regarding PGE2 and PGF2-alpha, and again the prevention of the stimulatory effect of PGE1 alone on RR. These data suggest that: the resting activity of the renin-angiotensin system (RAS) and the adenylate cyclase-cAMP system (AC-cAMP) of the hibernating ground squirrel is comparable to that of NH species; in contrast, the sensitivity of the RAS of the hibernator to PG stimulation is less than that exhibited by the RAS of NH species when comparable in vitro concentrations of three major PG's are used; PGE1 stimulation of RR in the hibernator is independent of changes in tcAMPc; changes in tcAMPc may be inversely related to those in RR in the hibernator; and the known stimulatory effect of PG's on the renal cortical AC-cAMP of NH species is not seen in the hibernating ground squirrel at comparable PG doses.

Adenylyl Cyclases↗
PubMed1985

Dietary sodium deficiency potentiates the effect of prostaglandin E2 on in vitro renin release in the rat.

Using a renal cortical slice system from sodium loaded (SL) or sodium deficient (SD) rats, this study investigated whether the effect of prostaglandin E2 (PGE2) on renin release (RR) is mediated by tissue cyclic AMP content (TcAMPc) changes, and if it can be modified by dietary sodium manipulation. At 10(-5) M, PGE2 significantly stimulated RR and TcAMPc in both SL and SD groups of slices. PGE2 doses of 10(-9) M and 10(-7) M were ineffective, although RR, but not TcAMPc, was significantly greater in the SD group in response to 10(-7) M PGE2 than RR in the SL group. Addition of the phosphodiesterase inhibitor theophylline (10(-4) M) together with the same three PGE2 doses maintained the stimulatory effect of 10(-5)M PGE2 alone on RR and TcAMPc in both groups of slices, and reversed the effect of 10(-7) M PGE2 alone on RR and TcAMPc in the SD group of slices only. Added by itself, theophylline was ineffective. These data indicate that: PGE2 can stimulate RR by a direct effect on the juxtaglomerular cells; the RR responses to PGE2 and theophylline administration are enhanced in the SD state; and the possibility of cAMP mediation of the effect of PGE2 on RR is discussed.

Animals↗
PubMed1978

Effect of norepinephrine on renin release and the cyclic AMP content of rat kidney slices: modification by sodium deficiency and alpha-adrenergic blockade.

The effect of L-norepinephrine (NE) on renin release by slices of kidney cortex from sodium-replete and sodium-deficient rats was studied in vitro. The rate of renin release by slices from sodium-deficient rats in the absence of added NE increased in proportion to the length of dietary sodium restriction and was significantly greater at all times than release by slices from sodium-replete animals. NE added to slices from the sodium-replete animals in concentrations ranging from 2 X 10(-9) to 2 X 10(-4)M caused a significant renin release only at a concentration of 2 X 10(-7)M. In contrast, the rate of renin release by slices from the sodium-deficient rats increased in a dose-related fashion when the NE concentration ranged from 2 X 10(-12) to 2 X 10(-7)M. NE in a concentration of 2 X 10(-5) had a lesser stimulatory effect, and 2 X 10(-4)M caused a significant inhibition of renin release. This inhibition was converted to stimulation by addition of the alpha-adrenergic blocking drug phentolamine. Phentolamine by itself was ineffective. The increases and decreases in renin release produced by NE were, in general, accompanied by increases and decreases in the cyclic AMP content of the slices. The changes in renin release were linear for 60 min, but the changes in cyclic AMP content were greater at 5 and 20 min than at 60 min. A dose-response relationship between the changes in renin release and cyclic AMP content was not observed. These data indicate that sodium deprivation enhances the sensitivity of the renin-secreting cells to catecholamine stimulation, and are consistent with the hypothesis that the increase in renin secretion produced by NE is mediated via cyclic AMP. The data also indicated that in high concentrations, NE exerts an inhibitory effect on renin release, and that this effect is mediated via stimulation of alpha-adrenergic receptors.

Animals↗