Hypervariable microsatellite for genetic diagnosis.
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Alleles↗
Biomedical subjects
J L Hall
Publications and source records attributed to J L Hall.
The role of the 5-HT2 receptor in the regulation of sexual performance of male rats.
The present studies have attempted to evaluate the role of 5-HT2 receptors in the regulation of sexual behavior of male rats by determining the effects of 5-HT2 receptor antagonists, pirenperone, LY53857 and LY281067, and a 5-HT2 receptor agonist, DOI. The administration of 1 mg/kg s.c. pirenperone produced a total suppression of ejaculatory response and lower doses had no effect. However, the administration 0.1 mg/kg s.c. of either LY53857 or LY281067 restored ejaculatory capacity to rats that were unable to ejaculate and produced significant decreases in ejaculatory latency in rats with full sexual capacity. Although all of these agents are 5-HT2 antagonists, LY53857 and LY281067 lack the additional monoaminergic activity of pirenperone. Since the effects of pirenperone were opposite from the effects of the selective 5-HT2 antagonists, the suppressive effects of this agent were probably related to its other monoaminergic activity e.g. alpha 1 antagonist activity. This proposal was supported by the observation that the administration of prazosin, an alpha 1 antagonist, significantly increased ejaculatory latency and suppressed the stimulatory effects of LY53857. In contrast to the stimulatory effects of the selective 5-HT2 antagonists, the administration of DOI, resulted in a suppression of sexual performance, which was blocked by pretreatment with LY53857.
Amphetamines↗
Glucose enhancement of performance on memory tests in young and aged humans.
Recent findings indicate that glucose administration enhances memory processes in rodents. This study examined the effects of glucose on memory in humans. After drinking glucose- or saccharin-flavored beverages, college-aged and elderly humans were tested with modified versions of the Wechsler Memory Scale. Beverages and tests were administered in a counter-balanced, crossover design, enabling within subject comparisons. The major findings were: (1) glucose enhanced memory in elderly and, to a lesser extent, in young subjects; and (2) glucose tolerance in individual subjects predicted memory in elderly, but not in young subjects on both glucose and saccharin test days.
Adolescent↗
Use of peri-operative antibiotics in abdominal surgery: a criterion audit.
OBJECTIVE: To evaluate the peri-operative use of parenteral antibiotics in 100 patients undergoing abdominal surgery. METHOD: Prospective criterion audit. RESULTS: There is a need for the close monitoring of antibiotic usage within hospitals, because 39% of the patients received inappropriate antibiotic therapy.
Abdomen↗
Food-associated intoxicants.
The association of toxic substances with human foods has long been recognized. While intrinsic compounds appear during storage as a result of spoilage by chemical processes or by contamination with micro-organisms. In the numerous stages of food production from source to table there are many opportunities for contamination. This article reviews the wide spectrum of food-associated toxicants, outlining the mechanisms by which these substances reach the food products. To illustrate the diversity of these mechanisms, some notable examples of mass contamination of food are quoted. The presence of toxic substances in human food is, and will continue to be, a challenge for toxicologists, and a source of concern for the public, for industry, and for the scientific community.
Animals↗
Effects of D2-dopaminergic receptor stimulation on the lordotic response of female rats.
The effects of LY163502, a highly selective D2 dopaminergic agonist, on the lordotic response of ovariectomized, estrogen-treated rats were evaluated. LY163502, administered subcutaneously or orally, produced a significantly greater lordotic response than vehicle. LY175877 [the opposite (+) enantiomer] was found to be inactive. The effects of subcutaneous administered LY163502 were abolished by prior treatment with dopaminergic receptor antagonists such as haloperidol or cis-flupenthixol. These studies are supportive of the view that LY163502 can initiate and potentiate female sexual behavior by stimulating D2 type dopaminergic receptors. In contrast to the enhancement of lordotic response that was observed in nonreceptive female rats, LY163502 was found to have suppressive effects on lordotic response frequency of receptive (estrogen-progesterone-treated) female rats. Reductions in lordotic responding occurred in two dose ranges, above and below the dose range found to potentiate lordotic response. The maximal suppressive effect at the low dose range was observed at 250 pg/kg, SC. This reduction in lordotic responding was proposed to be associated with a selective dopaminergic autoreceptor activation, leading to a diminished dopamine release and expression of a dopamine-mediated behavior (i.e., lordotic response). The reduction of lordotic responding that was observed at higher doses (25 micrograms/kg-25 mg/kg) was associated with an induction of stereotypic behavior that may have disrupted the sexual response pattern.
Animals↗
Effects of D2-dopaminergic receptor stimulation on male rat sexual behavior.
The effects of selective D2-dopaminergic receptor stimulation with LY163502 on male rat copulatory behavior were evaluated. LY163502 (25 ng/kg to 25 micrograms/kg s.c.) produced increases in the percentage of sexually inactive rats displaying mounting behavior and ejaculating during the test period. Within this same dose range, LY163502 administration induced an increase in the percentage of non-ejaculator rats that were capable of ejaculation. These findings are viewed as evidence that LY163502 can initiate sexual behavior and lower the threshold for ejaculation. The effects of LY163502 were further evaluated in rats that were capable of ejaculation during the test period. LY163502 (25 ng/kg to 25 micrograms/kg s.c. or p.o.) induced significant reductions in ejaculatory latency. These effects were blocked by prior treatment with centrally active dopaminergic antagonists, RO 22-1319 and sulpiride, but not with a peripherally active antagonist, domperidone. LY163502 administration was also found to inhibit sexual behavior in low doses of 25 pg/kg-10 ng/kg s.c. and in a much larger dose of 25 mg/kg s.c. These inhibitory effects are viewed as behavioral manifestations of selective dopaminergic autoreceptor activation with low doses and as the disruption of sexual behavior by induction of intense stereotypic behavior with high doses.
Administration, Oral↗
Memory enhancement in elderly humans: effects of glucose ingestion.
Recent findings demonstrate that, in rats, posttraining injections of glucose can enhance subsequent memory performance. The purpose of this study was to extend these findings to an elderly human population by testing the hypothesis that acute increases in peripheral blood glucose levels would enhance performance on memory tasks. Eleven subjects ranging in age from 58 to 76 years participated in the study. A within-subject, repeated-measures design was used in which each subject was tested under two different glycemic conditions: with fasting blood glucose levels and with increased blood glucose levels. Blood glucose was manipulated via consumption of beverages sweetened with either saccharin or glucose powder. After beverage consumption, subjects took four tests from the Wechsler Memory Scale. Comparisons of performance under the two glycemic conditions showed that scores were higher after the glucose beverage on narrative memory tests and the total Wechsler Scale. Nine of the eleven subjects had higher total Wechsler Scale scores. These results contribute to the growing evidence that glucose metabolism should be considered in the study of memory processes. The implications of such relationships for age-related memory deficits are discussed.
Aged↗
Why a MeSH organization?
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Hospital Administration↗
Glucose effects on memory: behavioral and pharmacological characteristics.
Recent findings indicate that post-training glucose injections can modulate memory storage for inhibitory (passive) avoidance training. Experiment I extended these findings to determine whether glucose, like other memory modulating treatments, enhances memory storage when administered after training with low footshock and impairs memory storage after high footshock training. In Experiment I, male Sprague-Dawley rats were trained in a one-trial inhibitory avoidance task using either a brief footshock (0.5 mA, 0.7 s) or slightly more intense footshock kept on until escape (0.7 mA, mean escape latency = 3.4 s). Immediately after training, each rat received a subcutaneous injection of glucose (100 mg/kg). When tested for retention performance 24 h later, the glucose-injected animals exhibited enhanced retention performance for low footshock training and impaired retention for high footshock training. Experiment II determined whether pretreatment with adrenergic antagonists blocked the effects of glucose on memory. Pretreatment with the alpha- or beta-adrenergic receptor antagonists, phenoxybenzamine, or propranolol, respectively, had no effect on acquisition or retention in animals trained with the brief footshock and did not affect glucose facilitation of that memory. In animals trained to escape footshock, phenoxybenzamine did not attenuate the amnesia produced by glucose. Propranolol-pretreated animals had impaired retention whether or not they received post-training amnestic injections of glucose; glucose had no effect on retention in these amnestic animals. These findings add further support to the view that glucose release after training and treatment may represent a physiological response subsequent to epinephrine release in modulating memory storage processing.
Animals↗
The effects of training, epinephrine, and glucose injections on plasma glucose levels in rats.
Recent findings indicate that a post-training injection of glucose enhances memory storage, suggesting that release of glucose into plasma may mediate the effects of epinephrine and perhaps other treatments on memory. The present experiment examined the effects of handling, inhibitory (passive) avoidance training, epinephrine and glucose injections on plasma glucose levels in Sprague-Dawley rats. Handling produced a small, but significant, transient increase in plasma glucose above basal levels. Saline injections caused a similar increase in circulating glucose levels. Inhibitory avoidance training with high footshock (2.0 mA, 2.0 s) resulted in significant increases in plasma glucose levels above those of low (0.5 mA, 0.75 s) and unshocked animals suggesting that glucose release is responsive to inhibitory avoidance training. Subcutaneous injections of epinephrine (0.01-1.0 mg/kg), or glucose (10-1000 mg/kg) significantly elevated glucose levels above those of saline-injected animals in a dose-dependent manner. Memory facilitating doses of epinephrine and glucose resulted in increases in plasma glucose levels similar to those seen in rats trained with high footshock. Higher doses of epinephrine and glucose resulted in further increases in circulating glucose, to levels significantly greater than those of memory facilitating doses. These results suggest that memory modulation, both endogenous and in response to epinephrine injections, may be mediated in part by circulating glucose levels. Thus, the findings of these experiments support the view that circulating glucose levels regulate the efficacy of neural memory storage processes.
Animals↗
Central 6-hydroxydopamine and renal sodium retention in mineralocorticoid-treated rats.
Cerebroventricular administration of 6-hydroxydopamine attenuated the development of deoxycorticosterone hypertension in the rat but did not affect the initial period of renal sodium retention. However, escape from the sodium retention was greater in 6-hydroxydopamine-treated rats. These data support the hypothesis that destruction of central catecholamine-containing neurons influences the renal handling of sodium. The enhanced escape may lead to diminished total body sodium, which attenuates the development of deoxycorticosterone hypertension.
Animals↗
Three expressed sequences within the human beta-tubulin multigene family each define a distinct isotype.
This paper describes the isolation and complete sequence of a novel expressed human beta-tubulin gene (beta 2). The sequence is compared with that of two other expressed human beta-tubulin genes (M40 and 5 beta). All are encoded by four exons. Though the boundaries of each exon are absolutely conserved among the three genes, the intervening sequences differ considerably in size and sequence content. Two of the genes (M40 and 5 beta) contain one (M40) or ten (5 beta) members of the middle repetitive Alu family sequences within one of their intervening sequences. Comparison of the amino acid sequences encoded by each gene reveals a high level of homology overall, though there is significant divergence between the carboxy termini of two of the genes. The pattern of expression of each beta-tubulin gene has been studied in several different human cell lines using unique non-crosshybridizing probes derived from the 3' untranslated regions. Two of the genes, M40 and beta 2, are expressed at varying levels in all of the cell lines examined, though the level of expression of one of these genes parallels the other in most cases. The third gene, 5 beta, is detectably expressed only in cells of neural origin. Thus, distinct human beta-tubulin isotypes are encoded by genes whose exon size and number has been conserved evolutionarily, but whose pattern of expression may be regulated either co-ordinately or uniquely. Of the approximately 15 sequences contained in the human beta-tubulin multigene family, nine have now been sequenced fully. The overall composition of the multigene family and the evolutionary relationships among its various members are discussed.
Amino Acid Sequence↗
Structural features and restricted expression of a human alpha-tubulin gene.
The nucleotide sequence of a human alpha-tubulin gene (b alpha 1) is described. This gene is extensively homologous to a rat alpha-tubulin gene in its coding regions, 3'-untranslated region and, indeed, in segments of its largest intron. However, with the exception of three short conserved blocks of homology, the 5' flanking regions of the rat and human genes are unrelated. Hence, these genes each encoding an identical protein are transcribed under the influence of divergent promoters. Blot analyses using RNA from a variety of transformed cells derived from different tissues indicate that expression of the human alpha-tubulin gene is restricted to cells of neurological origin. Among neurological cell types b alpha 1 expression is further restricted to adherent cells that are morphologically differentiated. The data presented suggest that the b alpha 1 gene encodes a prominent neuronal and glial alpha-tubulin and that b alpha 1 expression is a function of the differentiated state of these cells.
Amino Acid Sequence↗
Effect of male antisperm antibodies on sperm fertilizability in vitro.
Male partners of 129 infertile couples were evaluated for antisperm factors by using the hamster zona-free ovum (HZFO) test. Sperm-agglutinating activity and antifertilization factors were assessed by adding the male partner's serum to donor sperm in the HZFO-serum antibody (HA) test. When patient's HZFO scores were less than 20% of the hamster ova fertilized, fertilization by patient's serum in the HA test. Of 13 samples that failed to fertilize any of the hamster ova, nine were antibody-negative, of which seven had at least one extremely deficient sperm parameter. Of the four men with positive serum, two had normal and one had abnormal semen (one did not have a complete semen analysis). These data emphasize the need to test male partners for a decline in fertilizing capacity, which is frequently related to the presence of serum antisperm factors. These tests could be used to identify paternal and maternal components (sperm and serum) that may hinder fertilization in fertilization programs.
Animals↗
Cerebral intraventricular 6-hydroxydopamine prevents vascular changes in the mineralocorticoid hypertensive rat.
The effect of cerebral intraventricular administration of 6-hydroxydopamine (6-OHDA) on blood pressure and vascular smooth muscle responsiveness in deoxycorticosterone acetate (DOCA)-treated rats was assessed. Rats treated with 6-OHDA and DOCA had significantly lower systolic blood pressures (142 +/- 8 mm Hg) than rats treated with DOCA alone (185 +/- 5 mm Hg). After 5 weeks of DOCA treatment, femoral arteries and aortae were excised from these rats, cut helically into strips, and placed in a muscle bath to record isometric force. Dose-response curves to serotonin were shifted to the left in femoral arteries from DOCA-treated rats compared to both control and 6-OHDA-DOCA-treated rats (ED50: DOCA = 6.8 X 10(-8) M, control = 27.9 X 10(-8) M, 6-OHDA-DOCA = 13.4 X 10(-8) M). Arachidonic acid, the prostaglandin precursor, produced greater maximal contractions in femoral artery strips of DOCA-treated rats (358 +/- 56 mg) than in those from controls (115 +/- 31 mg). The maximal response to arachidonic acid in arteries from 6-OHDA-DOCA rats (203 +/- 78 mg) was not different from control values. Ouabain produced a greater maximal response in aortic strips from DOCA rats (658 +/- 165 mg) compared to those from control (196 +/- 72 mg) or 6-OHDA-DOCA (309 +/- 87 mg) rats. We conclude that increased vascular responsiveness to serotonin, arachidonic acid, and ouabain in DOCA hypertensive rats is secondary to a central action of the mineralocorticoid.
Animals↗
Dopamine agonist-induced hyperglycemia in rats: structure-activity relationships and mechanisms of action.
The concentration of blood glucose was measured in rats after administration of a number of drugs characterized as dopamine agonists. Compounds that cause release of dopamine, or agents that block the reuptake of dopamine, did not elevate blood glucose. Some direct dopamine receptor stimulants (lergotrile, bromocriptine, apomorphine) caused hyperglycemia, but other agonists (e.g. pergolide) did not. Further experiments with lergotrile, the most active hyperglycemic dopamine agonist, revealed that the blood glucose increase was accompanied by a marked elevation in liver glycogen, indicating a gluconeogenic effect of the compound. This hypothesis was supported by using inhibitors of gluconeogenesis (L-tryptophan or 3-mercaptopicolinic acid) to block lergotrile's hyperglycemic action. Structure-activity relationships among close analogues of lergotrile suggest that the cyano moiety in the lergotrile molecule may be of importance in the hyperglycemic action of lergotrile. These results indicate that central dopamine stimulation per se does not cause hyperglycemia in rats.
Animals↗
In vitro exposure of male and female mice gametes to cadmium chloride during the fertilization process, and its effects on pregnancy outcome.
The effect of cadmium chloride (Cd) on gamete fusion in vitro was evaluated, with further observations of the embryonic development and assessment of the pregnancy outcome of the in vitro fertilized mice. Oocytes were recovered from superovulated B6C3F1 females. Of 1210 control oocytes, 53.2% cleaved into two-cell stage embryos. Of these, 46.6% developed into blastocyst stage embryos which were then surgically transferred to pseudopregnant female CD-1 mice. Of a total of 63 implanted embryos, 8 (12.7%) developed in utero to live fetuses. Teratological examinations of these "test-tube" mice revealed no signs of abnormalities caused by in vitro culture. Male and female gametes were exposed to 0.4, 0.8, or 1.6 microM of Cd and a decrease in sperm motility was noted in the 1.6 microM group. Nevertheless, even in the highest concentration used, 56.4% of the ova cleaved into the two-cell stage, thus indicating no effect of Cd on initial gamete interaction. Gametes that had been treated with 0.4 and 0.8 microM Cd developed to blastocysts at rates comparable to that of the controls. In the 1.6 microM group, however, only one (3.2%) of the two-cell embryos developed to the blastocyst stage. Blastocysts from 0.4 microM Cd-treated gametes were then transferred to surrogate dams. Statistically significant blastocyst losses were recorded during the implantation period, whereas the pregnancy rate and the numbers of resorbed and live fetuses, were comparable to those of the controls. The offspring exhibited no malformations, and their body weights remained within the control values.
Animals↗