Nuclear-target effects in J/ psi production in 125-GeV/c antiproton and pi - interactions.
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Biomedical subjects
Publications and source records attributed to B Cox.
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The object of this study was to determine the reproducibility of the measurement of plasma catecholamine metabolites in normal control subjects and to assess the influence of factors such as time of day, diet, activity, blood pressure, and mood on the variance of these measures. Plasma free homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol (MHPG), and vanillylmandelic acid (VMA) were simultaneously measured by high performance liquid chromatography with electrochemical detection. Samples were collected from 15 doctors and nurses at 8 a.m. and at noon on 2 separate days. After the fasting 8 a.m. sample, the subjects ate a regular hospital breakfast. Activity in their usual tasks on an inpatient psychiatric unit was monitored electronically by an activity meter. Levels of each metabolite were not significantly different between days at the respective assay times and were highly correlated for individuals. MHPG showed a significant increase from morning to noon, while HVA showed a significant decrease. Activity, dietary intake of tyrosine and tyramine, blood pressure, pulse, scores on the Profile of Mood States, age, and sex were not related to plasma levels. The results demonstrate that measures of dopamine and norepinephrine metabolites have significant reliability in normal subjects in a setting used for research studies with psychiatric patients.
An eight month old girl was born with symmetrical bilateral oblique facial clefts and calcaneovarus foot deformity. CT scan of the head showed severe bilateral ocular hypoplasia and normal brain parenchyma. Peripheral blood karyotype showed a de novo balanced translocation between a chromosome 1 and 22. A submicroscopic imbalance secondary to this translocation cannot be ruled out. The pattern of the observed anomalies will help distinguish between oblique facial clefts and amniotic band disruption. Chromosomal studies should be performed in children with such rare malformations.
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Acanthonus armatus, a deep-water benthopelagic fish, has, per unit body weight, the smallest brain and largest semicircular canals of any known teleost and possibly any vertebrate. Pertinent areas of the brainstem and the cerebellum are large; this observation suggests that the fish's lateral line and vestibular senses are particularly acute. The huge cranial cavity also contains heavy saccular otoliths, which may indicate that the fish is sensitive to low-frequency sound. Brain size and specialization are consistent with an apparent pattern of low energy requirement, hovering and slow movement over the deep-sea floor, and consumption of small benthic prey in a dark environment.
A series of 2-[(2-aminoethyl)thio]quinolines substituted at the 3-position with alkyl, aryl, or heteroaryl groups has been prepared in the search for novel and selective 5-HT2 antagonists. The affinity of the compounds for 5-HT1 receptor sites was measured by their ability to displace [3H]-5-HT from rat brain synaptosomes whereas the affinity for 5-HT2 receptor sites was measured by their ability to displace [3H]spiperone from synaptosomes prepared from rat brain cortex. The 5-HT2 antagonist properties of the compounds were measured in vivo by their antagonism of 5-hydroxytryptophan-induced head twitches in the mouse and by their antagonism of hyperthermia induced by fenfluramine (N-ethyl-alpha-methyl-m-(trifluoromethyl)phenethylamine hydrochloride) in the rat. The structure-activity relationships in this series are discussed and the properties of 2-[[2-(dimethylamino)ethyl]thio]-3-phenylquinoline hydrochloride (70) are highlighted.
Recent studies suggest that opioid peptides may be involved in modulating the hypothalamus-pituitary-gonadal axis at a variety of levels in both males and females. We report here the presence of mRNA coding for the opioid peptide precursor prodynorphin in rat ovary, uterus, and testis. Expression of this opioid peptide precursor gene is compared to expression of two other opioid peptide precursor genes, proenkephalin and proopiomelanocortin, in mammalian reproductive tissues. Immunohistochemical analysis reveals that in the rat testis, prodynorphin-derived peptides are present in Leydig cells. The distribution of dynorphin immunoreactivity in various reproductive tissues was determined. Male reproductive tissues of the rat, rabbit, and guinea pig as well as rat ovary and uterus all contain detectable levels of dynorphin immunoreactivity. These observations suggest that prodynorphin-derived peptides may exert paracrine and/or autocrine effects in mammalian reproductive tissues.
Analysis of mortality and incidence rates over a 30-year period discloses differing trends in the risk of cervical cancer in older and younger women. Age-specific rates have been declining in older women, but there has been a marked rise in incidence among women under 40. Birth-cohort analyses show declining risks in successive cohorts of women born from late in the last century until the 1930's, except that risks were slightly elevated in the generation who were young adults during the Second World War. The risk of cervical cancer has increased very rapidly in cohorts born since the 1930s. A mathematical model suggests that women born around 1957 may have over three times the risk experienced by women born around 1932. The numbers of New Zealand women developing, and dying from, cervical cancer will increase strikingly over the next few decades unless effective control measures are introduced.
From January, 1981 through June, 1982 specimens from 21 patients with bladder (urothelial) cancer were placed in tissue culture, and one long term cell line was established (5%). From July, 1982 through February, 1984, using an improved culture medium, seven long term cell cultures were established from 21 patients (33%). In addition, one long term culture from a patient with a bladder melanoma was established using the standard culture medium. The nine cell cultures were derived from the following types of tumors: transitional cell carcinoma (6), adenocarcinoma (1), squamous cell carcinoma (1) and melanoma (1). All of the cell lines have produced tumors in athymic nude mice except for one transitional cell carcinoma. All of the cultures demonstrate aneuploidy. Homogeneously staining regions have been seen in some cell cultures. A common marker chromosome has not been identified.
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The rotational behaviour induced by 5-HT agonists has been investigated in rats with lesions of the dorsal raphe' nucleus (DRN). We have previously reported that 5-methyoxy-N,N-dimethyl-tryptamine (5-MeODMT) caused dose-related contralateral rotation in rats with 5,7-dihydroxytryptamine (5,7-DHT) lesions of the DRN. Similar findings are now presented for the 5-HT1 agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and 5-methoxy-3 (1,2,3,6-tetrahydropyridin-4-yl) (1H indole) (RU24969). In this model, in agreement with the behavioural studies, both agonists were shown to have a greater affinity for the 5-HT1 binding site when compared with the 5-HT2 binding site. Antagonist studies using selective 5-HT2 antagonists (ketanserin and pirenperone) at non-sedative doses failed to inhibit this behaviour. In contrast, the classical 5-HT antagonist methysergide caused significant inhibition of the rotational behaviour. These results suggest that 5-HT agonist-induced rotation in the rat is mediated via 5-HT1 receptors, probably located in the substantia nigra.
1. Intrahypothalamic injection of either 5-hydroxytryptamine (5-HT) (20 mug) or tryptamine (1 mug) caused hypothermia and hyperthermia respectively in lightly restrained rats maintained at an ambient temperature of 20 +/- 1 degrees C.2. Both the 5-HT- and the tryptamine-sensitive sites were located within the same region of the preoptic area.3. When rats were tested at different ambient temperatures (4, 20 and 29 degrees C), intrahypothalamic injection of 5-HT caused a marked fall in core temperature (-1.3 degrees C) in rats maintained at 4 degrees C, but smaller responses were obtained at 20 and 29 degrees C (-0.9 and -0.5 degrees C respectively). Tryptamine caused a significant hyperthermia in rats kept at 20 degrees C, but had no significant effect in rats maintained at either 4 or 29 degrees C.4. The hypothermic effect of 5-HT was selectively antagonized by systemic pre-treatment with cyproheptadine (2.5 mg/kg), but not by methergoline (0.625 mg/kg) and methysergide (0.2 mg/kg). In contrast, the hyperthermic effect of tryptamine was blocked by methergoline and methysergide, but not by cyproheptadine.5. Cyproheptadine (2.5 mg/kg) reduced the ability of rats to cope with a heat load but had no effect on the response to cold. In contrast, methergoline (0.625 mg/kg) and methysergide (0.2 mg/kg) reduced the ability to cope with cold but the rats' ability to cope with a heat load remained intact.6. These results suggest the existence of two indoleamine pathways within the preoptic anterior hypothalamus involved in the control of body temperature: a serotonergic pathway mediating heat loss and a non-serotonergic pathway mediating heat gain. The non-serotonergic system may exert its effects by modulating the activity of a central serotonergic system.
We tested, in rat liver, the postulate that free polysomes were precursors of membrane-bound polysomes. Three methods were used to isolate free and membrane-bound ribosomes from either post-nuclear or post-mitochondrial supernatants of rat liver. Isolation and quantitation of 28 S and 18 S rRNA allowed determination of the 40 S and 60 S subunit composition of free and membrane-bound ribosomal populations, while pulse labeling of 28 S and 18 S rRNA with [6-14C) orotic acid and inorganic (32P] phosphate allowed assessment of relative rates of subunit renewal. Throughout the extra-nuclear compartment, 40 S and 60 S subunits were present in essentially equal numbers, but, free ribosomes contained a stoichiometric excess of 40 S subunits, while membrane-bound ribosomes contained a complementary excess of 60 S subunits. Experiments with labeled precursors showed that throughout the extra-nuclear compartment, 40 S and 60 S subunits accumulated isotopes at essentially equal rates, however, free ribosomes accumulated isotopes faster than membrane-bound ribosomes. Among free ribosomes or polysomes, 40 S subunits accumulated isotopes faster than 60 S subunits, but, this relationship was not seen among membrane-bound ribosomes. Here, 40 S subunits accumulated isotope more slowly than 60 S subunits. This distribution of labeled precursors does not support the postulate that free polysomes are precursors of membrane-bound polysomes, but, these data suggest that membrane-bound polysomes could be precursors of free polysomes.
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The turning behaviour induced by 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) has been investigated in rats with lesions of the dorsal raphé nucleus (DRN). 5-MeODMT caused a dose-related contralateral turning in rats with 5,7-dihydroxytryptamine (5,7-DHT) lesions of the substantia nigra and a similar effect was observed in DRN-lesioned rats. In contrast, a dose-related ipsilateral turning was observed when 5-MeODMT was injected into rats with 5,7-DHT lesions of the striatum. These results suggest that the effects of 5-MeODMT in DRN-Lesioned rats are mediated via the substantia nigra. The contralateral turning induced by 5-MeODMT in rats with a 5,7-DHT lesion of the DRN was significantly reduced when a second 5-hydroxydopamine lesion was placed in the striatum, but not when it was placed in the nucleus accumbens. Thus the nigrostriatal dopaminergic system seems to be involved in 5-MeODMT-induced turning. The release of tritium from slices of substantia nigra previously labelled with [3H]-dopamine was inhibited by 5-MeODMT (10(-7) to 10(-5) M) and this effect was blocked by methysergide in a concentration-related manner. Tetrodotoxin (10(-7) M) failed to antagonise 5-MeODMT. These results suggest that 5-MeODMT can inhibit dopamine release from nigral dendrites, which could in turn enhance nigrostriatal activity by reducing the auto-inhibitory actions of dopamine, thereby causing contralateral turning in DRN-lesioned rats.
Tryptamine produced a concentration-related inhibition of potassium-evoked release of tritium from slices of rat hypothalamus preloaded with 3H-serotonin. This effect of tryptamine was blocked by a series of serotonin antagonists with a relative order of potency which suggested that tryptamine was acting on a post-junctional serotonin receptor. However, the response to tryptamine was also blocked by tetrodotoxin, indicating that tryptamine may be acting indirectly via the release of a second neurotransmitter. The finding that physostigmine enhanced, whilst atropine antagonised the effect of tryptamine suggests that the second neurotransmitter may be acetylcholine. This possibility is discussed.
The effect of a series of indoleamines on the potassium-evoked release of previously accumulated [3H]serotonin from slices of rat raphe nuclei has been studied. Indoleamine agonists produced a dose-related inhibition of potassium-evoked tritium release which was reversed by methiothepin, metergoline, mianserin and methysergide but not cyproheptadine or cinanserin. The relative order of antagonist potency for this effect was different from that obtained for the antagonism of indoleamine-induced inhibition of potassium-evoked tritium release from rat striatal slices previously loaded with [3H]-dopamine. The results show that the serotonin-autoreceptor located on cell bodies and dendrites in the raphe nucleus is different from the postsynaptic serotonin receptor located on dopamine nerve terminals in the striatum.