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Biomedical subjects

J L Hill

Publications and source records attributed to J L Hill.

At least 19 recordsLinked to original sources
PubMed1995

Evidence that 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced hyperthermia in rats is mediated by stimulation of 5-HT2A receptors.

The effects of various 5-HT receptor subtype-selective antagonists were studied on phenylisopropylamine hallucinogen 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced hyperthermia in Wistar rats, in an attempt to characterize the 5-HT receptor subtype mediating DOI-induced hyperthermia. Intraperitoneal administration of DOI to rats produced hyperthermia with a peak effect at 60 min. Pretreatment with propranolol (beta-adrenoceptor antagonist that also has binding affinity for 5-HT1A, 5-HT1B and 5-HT2C sites), MDL-72222 or ondansetron (5-HT3 antagonists) did not attenuate DOI-induced hyperthermia. In contrast, pretreatment with metergoline (5-HT1/5-HT2 antagonist), ketanserin, LY53857, mesulergine, mianserin and ritanserin (5-HT2C/5-HT2A antagonists), as well as spiperone (5-HT1A/5-HT2A/D2 antagonist), significantly attenuated DOI-induced hyperthermia. Furthermore, daily administration of DOI (2.5 mg/kg per day) for 17 days did not produce either tolerance to its hyperthermic effect or modify m-CPP-induced hyperthermia in rats. These findings suggest that DOI-induced hyperthermia in rats is mediated by stimulation of 5-HT2A receptors.

Amphetamines↗
PubMed1995

Oviduct proteins in fertilization and early embryo development.

The oviduct controls the environment in which the gametes are transported and fuse, and in which embryonic development begins. The ultrastructural topography of the ampulla and isthmus is similar, consisting of ciliated and secretory cells, but a different array of proteins is secreted by each segment along with various serum components. Amino acids are selectively secreted by the oviduct; these amino acids probably interact with the gametes or embryo to facilitate the processes of fertilization and development. An oviduct-specific glycoprotein is synthesized by the ampulla of sheep and cattle in response to oestrogen and secreted mainly from day-1 to day 3 of the ovarian cycle. This oestrus-associated glycoprotein (EGP) has a variable molecular mass of 80-97 kDa and a pI value ranging from 4.7 to 5.5. The bovine (b) and ovine (o) EGP genes are 95.5% identical and consist of 1560 base pairs encoding 519 amino acids containing one N-linked and several O-linked glycosylation sites. The terminal glycosides are N-acetylglucosamine and galactose-N-acetylgalactosamine for bEGP, and fucose, galactose and sialic acid residues are also identified for oEGP. EGP binds to zona pellucida and blastomere membranes, but evidence for EGP binding to sperm membranes is equivocal. After in vitro fertilizaton the proportion of sheep oocytes cleaving was increased in the presence of oEGP, but when single-cell embryos were cultured with oEGP, these cleavage rates were reduced. In addition, consistent positive effects of oEGP were observed on blastocyst formation. Elaboration of the mechanism of synthesis of EGP, its action and its role in fertilization and embryo development is important for our understanding of the events of early pregnancy.

Amino Acids↗
PubMed1994

Serum antibody for somatostatin-14 and prodynorphin 209-240 in patients with obsessive-compulsive disorder, schizophrenia, Alzheimer's disease, multiple sclerosis, and advanced HIV infection.

Patients with obsessive-compulsive disorder (OCD) demonstrated significant levels of antibody for somatostatin-28, its C-terminal fragment somatostatin-14, and prodynorphin. In contrast there were lower levels of reactivity for somatostatin-28(1-14) (the N-terminal fragment of somatostatin-28) and negligible reactivity for several other peptides including beta-endorphin and corticotropin. Healthy volunteers and disease controls [schizophrenia, Alzheimer's disease, multiple sclerosis, and subjects with advanced human immunodeficiency virus (HIV) infection] exhibited negligible reactivity. These data raise the consideration of an autoimmune mechanism for some OCD.

Adult↗
PubMed1994

Co-culture, oviduct secretion and the function of oviduct-specific glycoproteins.

Co-cultures of embryos with somatic cells, usually in the form of monolayers, or conditioned medium from these somatic cells, results in development past the early stage blocks and the formation of hatched blastocysts. Optimum rates of development are not achieved, however, and the task is to investigate components of the oviduct that are obligatory or facilitative for embryo development. Glycine and alanine are amino acids present in much higher concentrations in oviduct fluid than in serum or culture media. Glycoproteins specifically produced by the oviduct around oestrus bind to embryos and aid development but are absent from most culture media. These glycoproteins are induced by oestrogen in vivo but not in vitro. It is our contention that co-cultures of mammalian embryos should include appropriate concentrations of amino acids and a source of embryotrophic glycoproteins as an additive or by including stromal cells in addition to epithelial cells.

Animals↗
PubMed1994

Scopolamine effects on the pressor response to thyrotropin-releasing hormone in humans.

Thyrotropin-releasing hormone (TRH) produces a marked pressor effect, which may be mediated by central cholinergic neurons, which in turn enhance sympathetic nervous system activity. In this study, 22 subjects (10 patients with Alzheimer's disease and 12 elderly controls) were administered IV scopolamine or placebo prior to administration of IV high-dose TRH (0.5 mg/kg). Systolic blood pressure was less on the day scopolamine was administered prior to TRH administration, as compared with placebo (F[1,20] = 6.12, p < 0.02). Results indicate that the pressor effect of TRH is attenuated by scopolamine, indicating a role of the cholinergic system in this response in humans.

Aged↗
PubMed1994

Functional and biochemical evidence for altered serotonergic function in the fawn-hooded rat strain.

Administration of various doses of DOI (a 5-HT2A/5-HT2C agonist) produced hyperthermia that was significantly less in the FH rat strain relative to the Wistar rat strain. Similarly, administration of various doses of ipsapirone (a 5-HT1A agonist) produced hypothermia that was significantly less in the FH rat strain relative to the Wistar rat strain. Furthermore, m-CPP (a 5-HT agonist)-induced increases in growth hormone levels were also significantly less in the FH rat strain relative to the Wistar rat strain. There was no significant difference in the levels of either 5-HT or 5-HIAA between the two rat strains in the frontal cortex, hippocampus, hypothalamus, and striatum. In the brain stem, however, both 5-HT and 5-HIAA levels were significantly lower in the FH rat strain relative to the Wistar rat strain. On the other hand, 5-HT turnover rate was significantly higher in the hypothalamus and striatum and significantly lower in the hippocampus in the FH rat strain relative to the Wistar rat strain. These findings provide further evidence for altered serotonergic function in the FH rat strain and, in addition, suggest that the FH rat strain may prove to be a useful genetic model for some neuropsychiatric disorders with possible abnormalities in serotonergic function such as depression, obsessive-compulsive disorder, and the eating disorders.

Amphetamines↗
PubMed1994

Enhanced anorexic responses to m-chlorophenylpiperazine during lithium administration to fawn-hooded rats.

In the present study, we investigated whether functional adaptational changes in the serotonergic neurotransmitter mechanisms regulating food intake following long-term lithium treatment in Fawn-Hooded rats (a rat strain suggested to represent a genetic model of depression) were different or similar to those previously observed in Wistar rats. Long-term (21-25 days) lithium treatment accentuated m-chlorophenylpiperazine (m-CPP, a 5-HT agonist) induced decreases in food intake. There was no significant difference in either brain m-CPP concentrations or hypothalamic norepinephrine, dopamine and 5-hydroxyindoleacetic acid concentrations between control and long-term lithium-treated rats following m-CPP. However, hypothalamic serotonin concentrations were significantly higher in long-term lithium-treated compared to saline-treated animals. This finding contrasts with our previous report demonstrating attenuation of m-CPP-induced anorexia in Wistar rats following similar long-term lithium treatment, and therefore suggests a differential adaptation in the serotonergic neurotransmitter mechanisms regulating food intake in a genetic animal model of depression.

Animals↗
PubMed1994

Lithium treatment restores clonidine's effect in an animal model of depression.

IP administration of various doses of clonidine produces significant increases in growth hormone levels in the Wistar rats but not in the Fawn-Hooded (FH) rats, a rat strain suggested to be a genetic model of depression. However, short-term lithium treatment restores clonidine's effect on growth hormone levels in the Fawn-Hooded rats. Potentiation of clonidine's effect on growth hormone levels following short-term lithium treatment appears most likely due to increased serotonergic function as a consequence of enhanced 5-HT concentrations at postsynaptic 5-HT1C receptor sites. Thus, the reversal of a deficit state in Fawn-Hooded rats by lithium treatment supports earlier studies suggesting this rat strain to represent a genetic model of depression.

Animals↗
PubMed1994

Behavioral responses to intravenous meta-chlorophenylpiperazine in patients with seasonal affective disorder and control subjects before and after phototherapy.

A comparison of the baseline and post-infusion effects of the serotonin agonist meta-chlorophenylpiperazine (m-CPP) in 10 patients with seasonal affective disorder (SAD) and 11 healthy control subjects revealed significantly different subjective response profiles between the groups. Several baseline and m-CPP-stimulated responses in symptoms putatively related to serotonergic function changed significantly after a week's exposure to phototherapy in the SAD patients but not the control subjects. Before phototherapy, depressed patients with SAD reported activation-euphoria responses to m-CPP and significant decreases in carbohydrate hunger, but insignificant changes in feeling slowed or sleepy, while control subjects reported no mood or appetite changes but significant increases in feeling slowed down following m-CPP. After phototherapy, which led to a significant reduction in baseline depressive symptom rating to near-euthymic levels in the SAD patients, almost all of the patients' responses to m-CPP were normalized and no longer differed from the control subjects' responses. These results provide evidence of a possible dysregulation in serotonergic neurotransmission in depressed SAD patients that normalizes following treatment with phototherapy.

Adult↗
PubMed1994

Attenuation of clonidine-induced growth hormone release following chronic glucocorticoid and 5-hydroxytryptamine uptake-inhibiting antidepressant treatments.

Administration of various doses of clonidine increased plasma growth hormone levels in male Wistar rats. Chronic hydrocortisone treatment produced significant decreases in ACTH levels as well as a significant attenuation of clonidine-induced increases in growth hormone levels. Similarly, chronic treatment with 5-HT uptake-inhibiting antidepressants such as fluoxetine, clomipramine and imipramine also significantly attenuated clonidine-induced increases in growth hormone levels. On the other hand, chronic treatment with clorgyline (monoamine oxidase type A-inhibiting antidepressant) and 5-HT agonists, such as m-chlorophenylpiperazine, 1-(2,5-dimethoxy-4- iodophenyl)-2-aminopropane and 8-hydroxy-2-(di-n-propylamino)tetralin, did not have any significant effect on clonidine-induced increases in growth hormone levels. These findings suggest that development of functional subsensitivity of either alpha 2-adrenergic heteroreceptors or 5-HT1C receptors mediating clonidine-induced growth hormone secretion following chronic treatment with glucocorticoids and 5-HT uptake inhibitors.

Animals↗
PubMed1994

Role of various 5-HT receptor subtypes in mediating neuroendocrine effects of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) in rats.

The phenylisopropylamine hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) produced dose-related increases in plasma concentrations of prolactin, adrenocorticotropic hormone (ACTH) and corticosterone but not growth hormone in rats. Pretreatment with metergoline (serotonin, 5-HT1/5-HT2 antagonist), ritanserin and mianserin (5-HT2A/5-HT2C antagonists) significantly attenuated DOM-induced increases in prolactin, ACTH and corticosterone, whereas mesulergine (5-HT2A/5-HT2C antagonist) pretreatment significantly attenuated DOM-induced increases in plasma prolactin and ACTH but not corticosterone. Pretreatment with propranolol (beta adrenoceptor antagonist that also has high binding affinity for 5-HT1A, 5-HT1B and 5-HT2C sites), MDL-72222 and ondansetron (5-HT3 antagonists) attenuated DOM's effect on plasma prolactin, but did not attenuate DOM-induced increases in either ACTH or corticosterone. On the other hand, spiperone (5-HT1A/5-HT2A/D2 antagonist) pretreatment significantly attenuated DOM-induced increases in ACTH but not corticosterone. These findings demonstrate involvement of 5-HT2A/5-HT2C and 5-HT3 receptors in mediating DOM-induced increases in plasma prolactin, whereas DOM-induced increases in ACTH appear to be mediated by stimulation of 5-HT2A receptors. DOM-induced corticosterone secretion appears to be mediated by stimulation of 5-HT2A and/or 5-HT2C receptors. DOM does not affect growth hormone secretion in rats.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1994

Evidence that 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane-induced hypophagia and hyperthermia in rats is mediated by serotonin-2A receptors.

The administration of various doses of the phenylisopropylamine hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) to rats produced dose-related decreases in 1-hr food intake in a food-restricted paradigm and in locomotor activity. DOM also produced dose-related increases in temperature. Pretreatment with propranolol [a beta adrenoceptor antagonist that also has high binding affinity for serotonin (5-HT) 5-HT1A, 5-HT1B and 5-HT2C sites], bemesetron or ondansetron (5-HT3 antagonists) did not attenuate either DOM-induced hypophagia or hyperthermia. In contrast, pretreatment with metergoline (a 5-HT1/5-HT2 antagonist) and ritanserin (a 5-HT2A/5-HT2C antagonist) significantly attenuated both DOM-induced hypophagia and hyperthermia. However, pretreatment with mesulergine (a 5-HT2C/5-HT2A antagonist) significantly attenuated DOM-induced hyperthermia but not hypophagia. On the other hand, spiperone (5-HT1A/5-HT2A/D2 antagonist) pretreatment significantly attenuated DOM-induced hyperthermia but accentuated DOM-induced hypophagia. Daily administration of DOM (1.0 mg kg-1 day-1) produced complete tolerance to its hypophagic effect by day 4 but did not produce cross-tolerance to m-chlorophenylpiperazine-induced hypophagia. In contrast, daily administration of DOM for 7 days did not produce either tolerance to its hyperthermic effect or modify m-chlorophenylpiperazine-induced hyperthermia in rats. These findings suggest that DOM-induced hypophagia and hyperthermia in rats are mediated by stimulation of 5-HT2a receptors.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1993

CSF somatostatin in Alzheimer's disease and major depression: relationship to hypothalamic-pituitary-adrenal axis and clinical measures.

Patients with Alzheimer's disease (AD) and major depression have been shown to have overlapping clinical symptoms and biological markers, including decreased concentrations of cerebrospinal fluid (CSF) somatostatin-like immunoreactivity (SLI), which may be related to alterations in the hypothalamic-pituitary-adrenal axis activity. As in prior studies, we found that CSF SLI was significantly decreased in a group of AD patients (N = 49) and a group of elderly patients with major depression (N = 18), as compared with 13 age-matched controls (F[2, 77] = 12.9, p < .001). In the present study, CSF SLI and CSF corticotropin-releasing factor correlated significantly within the group of AD patients (r = 0.49, p < .0004) and almost attained significance in the depressed patients (r = 0.47, p < .07). CSF SLI correlated significantly with urinary free cortisol within each patient group (r = -0.51, p < .03). Clinical measures of dementia severity and depression did not consistently correlate with CSF SLI in either patient group.

Aged↗
PubMed1992

Fluoxetine modulates G protein alpha s, alpha q, and alpha 12 subunit mRNA expression in rat brain.

Signal-transducing G proteins are central to the coordination of receptor-effector communication. We have explored the effects of long-term fluoxetine administration of G alpha s, G alpha i1, G alpha i2, G alpha o, G alpha q and G alpha 12 mRNA expression in various rat brain regions using reverse transcriptase-polymerase chain reaction (RT-PCR)-mediated cross-species partial cDNA cloning. Northern blot analysis, and RNase protection assay techniques. Fluoxetine decreased G alpha s mRNA in midbrain, while mRNA expression of the novel G protein alpha subunits, G alpha q and G alpha 12, was increased in neostriatum and frontal cortex. We conclude that in addition to post-translational modification, regulation of G protein function by antidepressant drugs may occur at the level of gene expression.

Animals↗
PubMed1992

3-(2-Carboxypiperazin-4-yl)propyl-1-phosphonic acid decreases NMDA receptor mRNA.

Expression of the N-methyl-D-aspartate receptor gene during long-term administration of competitive and non-competitive NMDA antagonists was studied in rat brain using antisense cRNA transcribed from reverse transcriptase-polymerase chain reaction (RT-PCR)-generated rat NMDA receptor cDNA. Unlike non-competitive antagonists, 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) markedly decreased NMDA receptor mRNA steady-state concentrations in frontal cortex and hippocampus. Our results are consistent with a regulation of the NMDA receptor at the level of gene expression.

Animals↗
PubMed1992

Evidence for involvement of 5-HT1C and 5-HT2 receptors in the food intake suppressant effects of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI).

Administration of various doses of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) to rats produced dose-related decreases in 1-h food intake in the food-deprived paradigm. Pretreatment with spiperone (5-HT1A/5-HT2/D2 antagonist), propranolol or CGP361A (beta-adrenoceptor antagonists that also have binding affinities for 5-HT1A and 5-HT1B sites) and MDL-72222 (5-HT3 antagonist) did not attenuate DOI-induced suppression of food intake. In contrast, pretreatment with metergoline (5-HT1/5-HT2 antagonist) completely blocked whereas mesulergine, mianserin and ritanserin (5-HT1C/5-HT2 antagonists) partially blocked DOI's effect on food intake. On the other hand, pretreatment with MDL-72222 but not with m-chlorophenylpiperazine (m-CPP) significantly potentiated DOI-induced suppression of food intake. Furthermore, the food intake suppressant effects of various doses of DOI were found to be similar in the Fawn-Hooded (FH) rat strain as compared to the Wistar rat strain. These findings suggest that DOI-induced suppression of food intake is mediated by stimulation of both 5-HT1C and 5-HT2 receptors.

Amphetamines↗
PubMed1992

Distribution of peripheral lymphocytes in Alzheimer patients and controls.

Deficient immunoregulation has been postulated to play a role in the pathogenesis of Alzheimer's dementia. Recently, lymphopenia was reported to be more prevalent in Alzheimer patients than in control subjects. In addition, a decreasing number of total lymphocytes was found to be significantly correlated with increasing severity of dementia. In an attempt to replicate these findings, we studied 55 Alzheimer patients and 41 healthy controls of comparable age and gender, but found no significant difference in the distribution of total lymphocytes between these groups. Furthermore, total lymphocytes were not significantly correlated with dementia severity. Our findings, therefore, do not lend further support to an immune hypothesis for Alzheimer's dementia.

Adult↗