Biomedical subjects

G M Alexander

Publications and source records attributed to G M Alexander.

At least 37 records · Page 2Linked to original sources

PubMed1997

Androgen-behavior correlations in hypogonadal men and eugonadal men. I. Mood and response to auditory sexual stimuli.

Mood and response to auditory sexual stimuli were assessed in 33 hypogonadal men receiving testosterone (T) replacement therapy, 10 eugonadal men receiving T in a male contraceptive clinical trial, and 19 eugonadal men not administered T. Prior to and after 6 weeks of hormone administration, men completed a mood questionnaire, rated sexual arousal to and sexual enjoyment of auditory sexual stimuli, and performed a dichotic listening task measuring selective attention for sexual stimuli. Mood questionnaire results suggest that T has positive effects on mood in hypogonadal men when hormone levels are well below the normal male range of values, but does not have any effects on mood when hormone levels are within or above the normal range. However, increased sexual arousal and sexual enjoyment were associated with T administration regardless of gonadal status. Eugonadal men administered T also increased in the bias to attend to sexual stimuli. In contrast, the comparison group of eugonadal men not administered T showed no mood or sexual behavior changes across the two test sessions. These data support a positive relationship between T and sexual interest, sexual arousal, and sexual enjoyment in men.

Administration, Sublingual↗

PubMed1997

Rewarding affective properties of intra-nucleus accumbens injections of testosterone.

On alternating days, adult male Long-Evans rats implanted with bilateral cannulas in the nucleus accumbens received intracerebral injections of testosterone in a water-soluble cyclodextrin inclusion complex (0.125, 0.25, or 0.5 microg/0.5 microl saline) or saline immediately prior to being confined for 30 min to 1 of 2 compartments of a place-preference apparatus. All rats received 8 days of pairings (4 hormone and 4 saline). On Day 9 the rats were given a 20-min test session during which they had access to all compartments of the apparatus. No hormone was injected prior to the test session. On the test day, rats spent significantly more time in the compartment previously paired with bilateral intra-accumbens injections of testosterone (0.25 and 0.5 microg/0.5 microl saline) than in the compartment previously paired with saline injections. The findings indicate that intra-accumbens injections of testosterone are sufficient to produce reward.

Affect↗

PubMed1997

Expression of cell-cycle regulators p27Kip1 and cyclin E, alone and in combination, correlate with survival in young breast cancer patients.

Mutations in certain genes that regulate the cell cycle, such as p16 and p53, are frequently found in human cancers. However, tumor-specific mutations are uncommon in genes encoding cyclin E and the CDK inhibitor p27Kip1, two cell-cycle regulators that are also thought to contribute to tumor progression. It is now known that levels of both cyclin E and p27 can be controlled by posttranscriptional mechanisms, indicating that expression of these proteins can be altered by means other than simply mutation of their respective genes. Thus, changes in p27 and cyclin E protein levels in tumors might be more common than previously anticipated and may be indicators of tumor behavior.

Adult↗

PubMed1996

Posttraining intrahippocampal estradiol injections enhance spatial memory in male rats: interaction with cholinergic systems.

Male Long-Evans rats received an 8-trial training session in a spatial water maze task, followed by a unilateral posttraining intrahippocampal injection of either estradiol (1.0 microgram/0.5 microliter) or saline. Retention was tested 24 hr later, and latency to escape was used as a measure of memory. Retention test escape latencies of rats given intrahippocampal injections of estradiol were lower than those of saline-treated rats, indicating an enhancement of memory. Intrahippocampal injections of estradiol delayed 2 hr posttraining did not affect retention. In Experiment 2, the memory enhancing effect of intrahippocampal injection of estradiol was blocked by peripheral administration of a subeffective dose (0.1 mg/kg) of the cholinergic antagonist scopolamine. Intrahippocampal injections of estradiol enhance memory in male rats, and estradiol may influence memory through an interaction with muscarinic cholinergic systems.

Animals↗

PubMed1994

Testosterone has rewarding affective properties in male rats: implications for the biological basis of sexual motivation.

Evidence from mammalian species, including humans, suggests that testosterone (T) enhances motivational aspects of sexual behavior, although the mechanism by which T exerts this effect is unknown. The hypothesis that increases in plasma T have rewarding affective properties was examined. Acute elevations of plasma T were induced in intact male rats by systemic administration of a recently developed testosterone-hydroxypropyl-beta-cyclodextrin inclusion complex that mimics pulsatile release of the hormone. In a conditioned-place-preference paradigm, rats displayed a preference for an environment previously paired with T administration (800 micrograms/kg and 1,200 micrograms/kg) as opposed to an environment paired with saline administration, indicating that T has rewarding affective properties. The findings suggest that T may enhance motivational aspects of mammalian sexual behavior by facilitating acquisition or expression of learned associations between environmental stimuli and sexual activity.

Affect↗

PubMed1994

Effect of plasma levels of large neutral amino acids and degree of parkinsonism on the blood-to-brain transport of levodopa in naive and MPTP parkinsonian monkeys.

We investigated the transport of levodopa from blood to brain in control and in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) parkinsonian monkeys by using intracerebral microdialysis. The degree of parkinsonism was established by the monkey's clinical score and its postmortem striatal dopamine level. We administered levodopa plus carbidopa either orally or by intravenous injection. We estimated the blood-to-brain transport of levodopa as the ratio of its concentration in the brain's extracellular fluid to that in arterial plasma. This ratio was reduced in the MPTP parkinsonian monkeys, and we found an inverse relationship between the monkeys' ability to transport levodopa from blood to brain and their degree of parkinsonism. The oral administration of a high-protein meal or the intravenous infusion of large neutral amino acids before the administration of the levodopa plus carbidopa reduced the transport of levodopa into the brain, as measured by microdialysate collected from the striatum. We found that in two animals an intraperitoneal injection of the beta-adrenergic agonist isoproterenol increased the blood-to-brain transport of levodopa. Pharmacologic manipulation of the transport of levodopa from blood to brain may offer a new strategy for the treatment of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1994

Beta 2-adrenergic agonist as adjunct therapy to levodopa in Parkinson's disease.

We studied the effect of the beta 2-adrenergic agonist albuterol on Parkinson's disease (PD) patients receiving chronic levodopa treatment. The albuterol-treated patients demonstrated reduced parkinsonian symptoms and an increased ability to tap their index finger between two points 20 cm apart, and were able to perform a "walk test" in 70% of their control time. Three patients currently on chronic albuterol therapy still show amelioration of their parkinsonian symptoms, and two have reduced their daily levodopa dose. This study suggests that beta 2-adrenergic agonists as adjunct therapy to levodopa may be beneficial in PD.

Aged↗

PubMed1994

Gender labels and play styles: their relative contribution to children's selection of playmates.

The relative contribution of gender labels and play styles (masculine or feminine) in playmate selection was evaluated in 60 children between the ages of 4 and 8 years using a novel interview measure. In the interview, when targets' gender labels and targets' play styles were presented as independent dimensions, children showed predicted sex differences in preferences for gender labels and for play styles (including toys, rough-and-tumble play, and activity level). However, when targets' gender labels and targets' play styles were presented as competing dimensions, boys of all ages chose female targets with masculine play styles over male targets with feminine play styles. In contrast, younger girls (4-5-year-olds) chose female targets with masculine play styles, whereas older girls (6-8-year-olds) chose male targets with feminine play styles. This suggests possible sex differences in the contribution of gender labels and of play styles in the development of children's preferences for same-sexed playmates.

Age Factors↗

PubMed1993

Changes in brain dopamine receptors in MPTP parkinsonian monkeys following L-dopa treatment.

Twenty-two monkeys (Macaca fascicularis) were utilized in this study. Ten animals were rendered parkinsonian with serial injections of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). Five of these parkinsonian monkeys received L-dopa/carbidopa treatment, and five animals did not. The remaining twelve animals did not receive MPTP. Eight of these animals received no L-dopa treatment, two animals were treated chronically with L-dopa/carbidopa and two animals received L-dopa/carbidopa only on the day of sacrifice. All animals were given weekly scored neurologic examinations throughout the study. Their movement was quantitated in an activity box. All animals were sacrificed by an overdose of sodium pentobarbital. The parkinsonian animals were sacrificed 107-355 days after their last MPTP injection. The brains were removed and frozen. Punch samples were taken from the caudate and putamen for tissue dopamine determination. Selected areas of the basal ganglia were cut into 20 microns sections for quantitative receptor autoradiography. The density of D1 and D2 receptors was evaluated in the basal ganglia of these animals at the level of the anterior commissure. For the D2 assay, total binding was determined using various concentrations of [3H]spiperone in buffer containing 300 nm mianserin. For the D1 assay, total binding was determined using various concentrations of [3H]SCH-23390. Tissue isotope concentration was determined from the autoradiographs. The MPTP parkinsonian monkeys showed a mean striatal dopamine depletion of 93.5% and a mean clinical score of 9.0. The untreated parkinsonian monkeys demonstrated an increase in the number of D2 sites as compared to controls. This increase was greatest in the lateral putamen.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1993

N-methyl-4-phenylpyridinium (MPP+) potentiates the killing of cultured hepatocytes by catecholamines.

The role of catecholamines in the toxicity of MPTP (N-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine) was explored. The killing of cultured hepatocytes by dopamine and 6-hydroxydopamine was enhanced following inhibition of glutathione reductase by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), a manipulation known to sensitize such cells to an oxidative stress. The participation of activated oxygen species in the cell injury under such circumstances was shown by the ability of catalase and the ferric iron chelator deferoxamine to protect the hepatocytes. The toxicity of catecholamines was also potentiated by the mitochondrial site I (NADH dehydrogenase) inhibitor rotenone. MPP+ (N-methyl-4-phenyl-pyridinium), the putative toxic metabolite of MPTP is also a site I inhibitor. Incubation of hepatocytes with MPP+ similarly potentiated the toxicity of 6-hydroxydopamine, dopamine, and norepinephrine under conditions where MPP+ alone or catecholamines alone did not kill cells. Hepatocytes that had accumulated dopamine from the medium were killed by a subsequent exposure to MPP+ in the absence of a catecholamine in the medium. Hepatocytes that had not been pretreated with dopamine were not affected by the subsequent exposure to MPP+. These data indicated that catecholamines render hepatocytes more susceptible to the toxicity of MPP+ and suggest that the presence of catecholamines in specific neurons in the brain may be related to the selective neurotoxicity of MPTP.

1-Methyl-4-phenylpyridinium↗

PubMed1993

Sex steroids, sexual behavior, and selection attention for erotic stimuli in women using oral contraceptives.

The relationship between sex steroids and sexual behavior was examined in 19 oral contraceptive users. Retrospective assessment of sexual attitudes were obtained and women completed daily ratings of sexual behavior and well-being for 28 days. Plasma levels of free testosterone (T), estradiol, and progesterone were measured at weekly intervals. In addition, women performed a novel selective attention task designed to measure the strength of the tendency to be distracted by sexual stimuli. Multiple regression analyses using average sexual behavior variables as dependent variables, and hormone levels sexual attitudes and well-being as predictor variables, showed that free T was strongly and positively associated with sexual desire, sexual thoughts, and anticipation of sexual activity. A role for T in attention to sexual stimuli was also supported by the positive correlation between free T and the bias for sexual stimuli in a subgroup of women. These results are consistent with the hypothesis that T may enhance cognitive aspects of women's sexual behavior.

Adolescent↗

PubMed1993

A fluoroscopy-based computed tomography scanner for small specimen research.

RATIONALE AND OBJECTIVES: A small-laboratory computed tomography (CT) system using a fluoroscopic system and a personal computer was fabricated and tested. The motivation for building this specimen scanner was to provide medical researchers with the capability of using CT as a practical tool in their research, as well as to provide an opportunity for hands-on CT instruction. METHODS AND MATERIALS: The CT system was constructed using mostly off-the-shelf items; however, the CT stage itself was custom fabricated and software development was necessary. In addition, a personal computer and a standard fluoroscopy system were used. RESULTS: The spatial resolution was found to match the 228-microns sampling limitation, yielding approximately 2 line pairs per mm. Iodine contrast sensitivity studies showed that 1% solution of 370 mg/ml iodine solution was easily detected (P = .05). CONCLUSIONS: A small CT scanner for specimen research can be economically constructed, and is capable of good performance. The authors found substantial interest on the part of small animal researchers involved in a wide variety of medical research.

Animals↗

PubMed1992

Changes in brain catecholamines and dopamine uptake sites at different stages of MPTP parkinsonism in monkeys.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been shown to produce parkinsonism in primates. We have studied the changes in brain catecholamines and the distribution of desipramine insensitive mazindol binding sites in MPTP parkinsonian primates at different levels of parkinsonism. Thirty-seven monkeys (Macaca fascicularis) were utilized in this study. Twelve naive animals received no treatment and served as controls. Twenty-five animals were rendered parkinsonian with serial injections of MPTP. All animals were given scored neurologic examinations throughout the study. Their movement was quantitated in an activity box. The animals were sacrificed 30-360 days after their last MPTP injection. The clinical exam of the MPTP parkinsonian monkeys demonstrated mildly to severely affected animals. There was an exponential decrease in brain catecholamine levels with increased clinical parkinsonism. The MPTP parkinsonian animals showed the greatest decrease (67-99.8%) in tissue dopamine levels in the caudate nucleus. The putamen followed closely in severity (48-99.8%) and the nucleus accumbens was much less affected (0-40%). The percent reduction of norepinephrine in the anterior pole of the frontal cortex (0-48%) was similar in degree to the decreased dopamine levels in the nucleus accumbens. Mazindol binding was decreased 30-98% in the caudate nucleus, 20-97% in the putamen, 0-26% in the nucleus accumbens, 80-96% in the substantia nigra pars compacta and 49-94% in the ventral tegmental area. In the striatum, the decreased mazindol binding was more pronounced laterally and posteriorly. In each animal, there was good correlation between tissue dopamine levels and the number of mazindol binding sites.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1992

Binary screen detector system for single-pulse dual-energy radiography.

Dual-energy radiographic acquisition performed with a single pulse of x rays has been limited to use of stacked detectors such as photo-stimulable phosphor plates. In this study, a binary screen system is introduced that enables single-pulse dual-energy acquisition with nonstacked detectors such as charge-coupled devices (CCDs). Two x-ray phosphors with different K edges, designed to emit light of different wavelengths, were bound together in a single screen. Two CCD cameras, each sensitive to the respective wavelengths emitted by each phosphor, are proposed to be coupled to the binary screen. Optical isolation and detection of the optical emissions from the screen would enable simultaneous acquisition of both low- and high-energy images, which can then be used in dual-energy subtraction. Computer simulation results and experimentally acquired images suggest that the binary screen approach may be a viable alternative to stacked detector technology for dual-energy radiographic imaging.

Computer Simulation↗

PubMed1991

Dopamine receptor changes in untreated and (+)-PHNO-treated MPTP parkinsonian primates.

Fifteen monkeys (Macaca fascicularis) were utilized in this study. Seven naive animals received no treatment and served as controls. Eight animals were rendered parkinsonian with serial injections of MPTP. Three of the parkinsonian monkeys were treated with (+)-4-propyl-9-hydroxynaphthoxasine [(+)-PHNO], a selective dopamine D2 agonist. (+)-PHNO (2-5 micrograms/kg/h) was administered continuously using subcutaneous osmotic pumps. All animals were given weekly scored neurologic examinations throughout the study. Their movement was quantitated in an activity box. The animals were sacrificed 30-120 days after their last MPTP injection by an overdose of sodium pentobarbital. The brains were removed, frozen and cut into 20-microns sections. The density of D1 and D2 receptors was studied in the basal ganglia of these animals at the level of the anterior commissure. For the D2 assay, total binding was determined using various concentrations of [3H]spiperone in buffer containing 300 nm mianserine. For the D1 assay, total binding was determined using various concentrations of [3H]SCH-23390. Tissue isotope concentration was determined from the autoradiographs. The parkinsonian animals demonstrated 90-97% dopamine depletion in the striatum. There was a 75-90% decrease in free movement in the untreated parkinsonian monkeys and their composite clinical score was 8.9 on a scale of 0-16 (zero being normal). Control monkey scores averaged 0.6. The untreated parkinsonian monkeys demonstrated an increase in the number of D2 sites as compared to controls. This increase was greatest at the lateral putamen. The (+)-PHNO-treated monkeys demonstrated increased activity, a neurologic score of 3.4, and a 40-70% decreased in D2 sites in both caudate and putamen. There was no change in the number of D1 binding sites in both the untreated and the (+)-PHNO-treated parkinsonian monkeys as compared to controls.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1991

Oral contraceptives, androgens, and the sexuality of young women: I. A comparison of sexual experience, sexual attitudes, and gender role in oral contraceptive users and nonusers.

Female undergraduates (108) volunteered for a study of hormones and sexuality, 55 of whom were oral contraceptive (OC) users. In this paper, OC users and nonusers are compared on measures of sexual attitudes and behavior, use of erotic fantasy, and gender role. In the second paper, the effects of OC on androgen levels and the relationship between androgens and behavioral measures within each group are reported. OC users were more likely to have a current sexual partner and less likely to be virgins. The two groups did not differ in frequency of masturbation or use of erotic fantasies. OC users reported less restrictive sexual morality and more interest in erotic images. These differences persisted when women without current partners were excluded. Among those in active sexual relationships, OC users reported more frequent sexual intercourse, higher psychosexual motivation and enjoyment, and were more positive in their evaluation of their partners than OC nonusers.

Adult↗

PubMed1991

Oral contraceptives, androgens, and the sexuality of young women: II. The role of androgens.

The relationships between plasma free testosterone (FT) and measures of sexual attitude, sexual behavior, and gender role behavior were assessed in 55 oral contraceptive-using and 53 nonusing female undergraduates. Plasma FT and other measures of androgenicity were substantially lower in the oral contraceptive (OC) group. Correlations between FT and certain behavioral and attitudinal measures were found in the OC users but not the nonusers. In the OC users, FT was positively associated with frequency of sexual intercourse but not with frequency of masturbation. It was negatively associated with restrictive sexual morality. Correlations between FT and measures of gender role behavior were negligible, and FT was unrelated to proceptivity, homosexual interest, or the use of sexual fantasy. The occurrence of some predicted correlations among pill-using women but not the nonusers requires explanation, particularly in view of the substantially lower levels of FT in the pill-using group. It is suggested that androgen-behavior relationships in women are easily obscured by psychosocial influences and in this sample of young women such influences may have been more powerful among those not using OCs. Such psychosocial influences are likely to differ at different stages of women's life cycles. The importance of controlling for such influences in any study of hormone-sexual behavior relationships in women is emphasized, and the need for prospective studies of women before and after starting on steroidal contraception is recognized.

Adult↗

PubMed1991

The association between testosterone, sexual arousal, and selective attention for erotic stimuli in men.

Twenty-six, eugonadal men between the ages of 18 and 27 participated in this investigation of the relationship between sexual arousal, testosterone (T) levels, and the processing of sexual information. At each of the two test sessions, subjects gave a blood sample, listened to an erotic or neutral priming audiotape, and completed a dichotic listening task designed to assess selective attention for sexual stimuli. Subjective levels of sexual arousal to the audiotape and sexual attitudes and sexual experience were assessed by self-report measures. Contrary to our hypothesis, there was no relationship between levels of free T and the strength of the selective attention bias for sexual stimuli. However, men who were more distracted by the sexual material in the task reported higher levels of sexual arousal to erotic imagery than men who were less distracted by the sexual material in the task (P less than 0.01). Moreover, men who were more sexually aroused by the erotic audiotape made significantly less shadowing errors in the erotic prime condition then they did during the neutral prime condition (P less than 0.05). There was a negative association between T and shadowing errors in the erotic prime condition (P less than 0.05). These results suggest that lower thresholds for sexual arousal are associated with a greater bias to attend to sexual information and that T may have effects on cognitive-motivational aspects of sexual behavior by enhancing attention to relevant stimuli.

Adolescent↗