Biomedical subjects

J Herbert

Publications and source records attributed to J Herbert.

At least 181 records · Page 10Linked to original sources

PubMed1987

Identification and isolation of two pentraxins from bovine serum.

Two distinct pentraxin proteins were isolated from bovine serum by calcium-dependent affinity chromatography on high pyruvate agarose gel. One of these proteins cross-reacted specifically with certain rabbit anti-human CRP antisera and was therefore designated as bovine CRP. The other cross-reacted specifically with a sheep anti-human SAP antiserum and was therefore designated as bovine SAP. Although the mixture of these two pentraxins was not resolved by gel filtration chromatography, they were separated by solid phase absorption of the CRP with immobilized rabbit anti-human CRP antibodies. Their identity as pentraxins was confirmed by their electron microscopic appearance. Bovine CRP was composed of a single type of non-glycosylated subunit whilst bovine SAP contained two major types of glycosylated subunits and a minor polypeptide, the glycosylation of which was not determined. Serum concentrations were in the range of 5-40 mg/l and neither protein behaved as an acute phase reactant. No bovine serum protein undergoing calcium-dependent binding to phosphoryl choline or pneumococcal C-polysaccharide was obtained.

Animals↗

PubMed1986

Neurotoxic lesions of the paraventriculo-spinal projection block the nocturnal rise in pineal melatonin synthesis in the Syrian hamster.

The paraventriculo-spinal projection of the Syrian hamster was characterized by retrograde labelling of neuronal perikarya in the paraventricular nucleus of the hypothalamus (PVN) following injection of True blue tracer into the intermediolateral cell column of the thoracic spinal cord. Injection of the excitatory neurotoxin, N-methyl-D,L-aspartic acid into the region of the PVN spared magnocellular neurones and fibres of passage but destroyed parvocellular neurones of the paraventriculo-spinal pathway. Hamsters bearing complete bilateral lesions of the parvocellular PVN failed to show the typical nocturnal increase in pineal melatonin content. These data indicate the importance of the paraventriculo-spinal projection in the central control of pineal melatonin synthesis.

Animals↗

PubMed1986

The effect of midazolam and beta-carboline carboxylic acid ethyl ester on behaviour, steroid hormones and central monoamine metabolites in social groups of talapoin monkeys.

Established social groups of talapoin monkeys show rank-related differences in aggressive, social and sexual behaviours and visual monitoring, as well as in endocrine and monoamine profiles. Here we describe the effects on these variables of an "anxiogenic drug", beta-carboline carboxylic acid ethyl ester (beta-CCE), and an anxiolytic drug (midazolam) given to either dominant or subordinate male talapoins. In dominant animals beta-CCE increased aggression and visual monitoring but reduced sexual behaviour. Treatment of subordinate animals with beta-CCE served only to increase visual monitoring. Conversely, treatment with a non-sedative acute dose of midazolam in dominants reduced aggressive behaviour and increased sexual behaviour, whereas in subordinates no behavioural changes were noted. Significant effects on endocrine and neurochemical variables were not seen with the acute drug treatments employed. Nevertheless, the results show that drugs which modulate anxiety produce status-dependent behavioural effects.

Aggression↗

PubMed1986

Endocrine responses and examination anxiety.

Endocrine and psychological function (measuring both affect and attitudes to study) were studied in 38 male medical students 4 weeks and 1-2 h before a major examination. Anxiety (or tension) and emotionality increased just before the examination, as did the 'denial' subscale of a 'coping' questionnaire. Serum cortisol and prolactin increased; serum testosterone and LH were unchanged. Both urinary noradrenaline and adrenaline were elevated. Increased cortisol correlated with increased prolactin across subjects; so, too, did levels of urinary noradrenaline and adrenaline, but the two sets of endocrine responses were not correlated with each other. Several of the trait scales predicted the endocrine response to the examination. The 'lie' scale of the Eysenck Personality Questionnaire correlated negatively with changes in both cortisol and prolactin, as did 'debilitating' anxiety, as defined by the Alpert-Haber scale. However, although there were no significant correlations between changes in hormone levels and those in any of the state scales, there was some relation between absolute hormone levels on the day of the examination. Measures of academic strategies or psychological responses to examinations do not predict the nature of the considerable hormonal response which occurs in this homogeneous set of high-achieving students.

Anxiety↗

PubMed1986

beta-Endorphin levels in the cerebrospinal fluid of male talapoin monkeys in social groups related to dominance status and the luteinizing hormone response to naloxone.

beta-Endorphin-like immunoreactivity was measured in the cerebrospinal fluid of 20 male talapoin monkeys living in mixed-sex social groups. It was shown that beta-endorphin was the major immunoreactive peptide; there was no evidence for high molecular weight precursors, or for either N-acetyl or C-shortened metabolites. Dominant males (those at the top of the social hierarchy) had lower levels of beta-endorphin than those of intermediate rank; subordinate males had higher levels than either of the other two ranks--about three times those measured in dominants. There were significant negative correlations between beta-endorphin in cerebrospinal fluid and both the amount of aggression given and sexual behaviour shown towards females. The response of the hypothalamo-pituitary system to opiate blockade was tested by giving the males naloxone in doses of 0.125, 0.25, 0.5, 1.0 and 5.0 mg/kg and assaying serum levels of luteinizing hormone 20 min later. Dominant males released significant amounts of luteinizing hormone at doses of 0.25 and higher; there was no release in either intermediate or subordinate monkeys at any dose. These findings show that an animal's rank in the social group in which it lives is strongly correlated with beta-endorphin levels in the cerebrospinal fluid, and with changes in the neuroendocrine response to opiate blockade. Altered opiate neural activity may be responsible for the depressed levels of sexual behaviour and gonadal function observed in monkeys at the bottom of the hierarchy.

Aggression↗

PubMed1986

Localization of immunoreactive transthyretin (prealbumin) and of transthyretin mRNA in fetal and adult rat brain.

We used a combination of immunohistochemical and molecular-biological techniques to investigate the localization of transthyretin (TTR) in the brains of adult and fetal rats. The immunohistochemical studies employed antibodies purified by immunosorbent affinity chromatography, permitting the specific staining and localization of TTR using the unlabeled peroxidase-antiperoxidase method. TTR mRNA levels were measured by Northern-blot analysis of poly (A+) RNA, followed by hybridization to 32P-labeled TTR cDNA; TTR mRNA was localized in brain tissue sections by in situ hybridization. Immunoreactive TTR was found to be specifically localized in the choroid plexus epithelial cells of adult rat brain. High levels of TTR mRNA were found in poly (A+) RNA samples obtained from the choroid plexus. In addition, the specific localization of TTR mRNA in the epithelial cells of the choroid plexus was demonstrated by in situ hybridization. Neither immunoreactive TTR nor TTR mRNA were found in other regions of adult rat brains. The levels of TTR mRNA in the choroid plexus were at least 30 times higher than those observed in the adult liver. Immunoreactive TTR was observed in the brains of fetal rats on as early as the 11th day of gestation. This immunoreactive TTR was localized in the tela choroidea, the developmental forerunner of the choroid plexus. Immunoreactive TTR was also observed in the fetal choroid plexus as it began to form (14th day of gestation) as well as in the more completely developed choroid plexus (18th day of gestation).(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1986

Modulation by social status of the relationship between cerebrospinal fluid and serum cortisol levels in male talapoin monkeys.

Serum and cerebrospinal fluid (CSF) cortisol were measured by radioimmunoassay in male talapoin monkeys living in social groups. The slopes of the regressions between cortisol in the two compartments were significantly less in dominant than either the most subordinate males or those of intermediate rank. Furthermore, the dominants' CSF also contained proportionately more cortisol than was predicted from the overall regression analyses of the groups of which they were members. There was no difference in the proportion of 'free' cortisol (that is, not bound to serum proteins) between the serums of dominant or subordinate males. These findings point to an association between social status and the distribution of cortisol between blood and CSF in these monkeys.

Animals↗

PubMed1986

Differences in blood levels of androgens in female talapoin monkeys related to their social status.

Serum testosterone and androstenedione levels were lower in the subordinate female talapoin monkeys of four social groups than either dominant or intermediate-ranking females. This was found in both intact or ovariectomized (oestrogen-treated) animals, which suggests that androgen from the adrenals contributed to this rank-related endocrine effect. These differences disappeared when the females were housed singly, levels in all animals becoming similar to those in subordinates in the group cage. There were no rank-related differences in progesterone levels during either the follicular or luteal phase of the cycle in intact females, or in those of ovariectomized females of different rank, but cortisol was highest in dominant group-living animals in these experiments. Significant correlations were found between androgen levels in group-living females and the amount of sexual interest shown in them by males; the amount of aggressive interaction involving each female did not correlate with her androgen levels. Social rank is defined according to the direction, not the amount, of aggression. These findings suggest that the social hierarchy regulates androgen levels in these female monkeys; there may also be effects on the ability of females to respond to their own, or to administered, androgen. Similar findings have been made previously in male talapoins. Since androgens fill a critical role in the sexual behaviour of both sexes in primates, this may be a neuroendocrine mechanism of general significance relating behaviour to social rank.

Androstenedione↗

PubMed1986

Transthyretin: a choroid plexus-specific transport protein in human brain. The 1986 S. Weir Mitchell award.

Plasma transthyretin (TTR, formerly called prealbumin) is a 55-kd protein that participates in the plasma transport of both thyroxine and retinol (vitamin A). TTR concentrations are disproportionately high in human ventricular CSF, suggesting that TTR is either selectively transported across or synthesized de novo within the blood-CSF barrier. To address this question, we adopted a molecular genetic approach; after isolating a cDNA clone encoding human TTR, we previously demonstrated specific TTR messenger RNA (mRNA) synthesis in rat choroid plexus. We have now extended these investigations to the human brain. Northern analysis of postmortem brain homogenates revealed abundant TTR mRNA in choroid plexus, but not in cerebellum or cerebral cortex. Choroid plexus mRNA was readily translated into TTR preprotein in an in vitro translation system. An immunocytochemical survey of human postmortem brain sections revealed the presence of TTR protein specifically and uniquely in the cytoplasm of choroid plexus epithelial cells; these results were corroborated at the mRNA level by an extensive survey of whole rat-brain sections by in situ hybridization. Therefore, within the mammalian CNS, TTR is the first known protein synthesized solely by the choroid plexus, suggesting a special role for TTR in the brain or CSF. Whether this function differs from its established plasma transport functions is presently unknown.

Animals↗

PubMed1986

Granulomatous brain tumor caused by Acanthamoeba. Case report.

A case of a previously healthy 7-year-old girl with a left frontoparietal tumor identified as an Acanthamoeba-induced granuloma is reported, and the literature on Acanthamoeba meningoencephalitis is reviewed. Unlike most reported cases, the Acanthamoeba central nervous system infection presented in this girl as a discrete tumor without meningeal involvement or diffuse encephalitis. A favorable outcome was obtained following total excision of the mass and treatment with ketoconazole.

Amebiasis↗

PubMed1985

Demonstration of transthyretin mRNA in the brain and other extrahepatic tissues in the rat.

Studies were conducted to ascertain if transthyretin mRNA was present in extrahepatic tissues of the rat. A trnasthyretin cDNA clone was isolated from a lambda gt11 human liver cDNA library by antibody screening and its identity was confirmed by nucleotide sequence analysis. This transthyretin cDNA clone was used to survey poly(A+) RNA isolated from 12 different rat tissues for transthyretin mRNA by Northern blot analysis. The liver contained the highest level of transthyretin mRNA and this level was not altered by the vitamin A status of the rat. A significant amount of transthyretin mRNA was found in the brain (30% of the level of the liver) which was localized in specific regions of the brain. In addition, detectable levels of transthyretin mRNA (1% to 2% of that of the liver) were observed in the stomach, heart, skeletal muscle, and spleen. Translation of brain poly(A+) RNA in rabbit reticulocyte lysates and immunoprecipitation of the translation products with anti-transthyretin antiserum resulted in a protein band of the same size as liver pre-transthyretin. Liver pre-transthyretin was processed by the cotranslational addition of dog pancreas microsomal membranes to a protein that migrated coincidentally with monomeric serum transthyretin. These data suggest that transthyretin in the brain and the cerebrospinal fluid results from de novo synthesis and that transthyretin may play a significant physiological function, as yet unknown, within the nervous system.

Animals↗

PubMed1985

Melatonin and the brain in photoperiodic mammals.

The reproductive cycle of photoperiodic species is driven by seasonal changes in daylength. The pineal gland transduces photic information into an endocrine signal. The duration of the nocturnal bout of melatonin secretion is a direct indicator of night-length. The circadian rhythm of melatonin production is driven by a multisynaptic pathway from the suprachiasmatic nuclei (SCN), via the parvocellular portion of the paraventricular nucleus to the preganglionic sympathetic neurons of the thoracic spinal cord. The melatonin signal acts as an interval timer. The cellular basis of the detection of the signal is unknown. The site of detection is possibly within the anterior hypothalamus. The SCN are not essential components of the system that responds to the pineal interval timer. Photoperiod and the pineal melatonin signal have pronounced effects on the function of endogenous opioids, which are probably related to changes in the neuroendocrine mechanisms that regulate gonadotropin release.

Animals↗

PubMed1985

Relationship between dominance hierarchy, cerebrospinal fluid levels of amine transmitter metabolites (5-hydroxyindole acetic acid and homovanillic acid) and plasma cortisol in monkeys.

The dominance hierarchy has repercussions for a monkey's sexual behaviour and endocrine state. Here we report on neural mechanisms that are sensitive to a monkey's status in the social hierarchy, and which may regulate not only its endocrine function but its sexual responsiveness to its own hormones. During the initial phase of group formation, 5-hydroxyindole acetic acid, the metabolite of serotonin, increases in the cerebrospinal fluid of monkeys which become subordinate (all groups), but decreases in monkeys which become dominant (two out of three groups) and shows no changes in intermediate-ranking animals (five out of seven). Homovanillic acid, a metabolite of dopamine, may also increase in the cerebrospinal fluid of monkeys that become subordinate (two out three groups). In the initial period of group formation these changes in transmitter metabolites do not parallel changes in cortisol. However, in the established social groups, both 5-hydroxyindole acetic acid and plasma cortisol are related to the social hierarchy, being greater in those monkeys that are subordinate, but homovanillic acid shows no consistent change. Although subordinate monkeys receive more aggression than others in their group, fluctuations in 5-hydroxyindole acetic acid do not correlate with aggressive behaviour, and are equally high on days when no aggression occurs. Dominant males, however, had higher 5-hydroxyindole acetic acid levels on days when they were involved in agonistic encounters. In the established social hierarchy therefore, elevated levels of the serotonin metabolite in cerebrospinal fluid seem reflect a "state"-dependent consequence of occupying a position of low social status.

Animals↗

PubMed1985

A novel cell type carrying both Th and Tc/s markers in the blood of cyclosporine-treated, allografted rats.

During treatment of heart-grafted rats with cyclosporine, an unusual large lymphocyte appears in the blood. These cells constitute up to 40% of the peripheral blood leukocyte population and carry both the T helper/DTH and T cytotoxic/suppressor differentiation antigens. They require both the allograft and CsA for their generation and are not recently thymus-derived. They gradually disappear after stopping CsA treatment, although the treated rats remain tolerant of the graft.

Animals↗

PubMed1985

Graft rejection in a congenic panel of rats with defined immune response genes for MHC class I antigens. I. Rejection of and priming to the RT1Aa antigen.

Allograft rejection in the rat has been shown to be under stringent immune response (Ir) gene control using major histocompatibility complex recombinant animals as donors. Presentation of an isolated class I antigenic difference to high responder recipients results in rapid graft rejection, but low responders fail to reject. This striking qualitative difference is also seen in some liver grafting experiments in which the donor presents a full MHC haplotype and minor antigen mismatch to the responders. Grafts of other organs, however, do not discriminate qualitatively between high and low responders when a full haplotype mismatch exists. We have used the canonical high and low-responder animals, (PVG X PVG-RT1u)F1 and PVG to examine whether any qualitative difference in responsiveness can be detected against the a haplotype using a variety of organ grafts. We have confirmed a qualitative difference between high and low responders using PVG.R1 donors presenting an isolated class I (Aa) difference. Rapid rejection by high responders contrasted with complete failure to reject by the low responders. No difference in rejection tempo was found when a full a haplotype mismatch was introduced. This could have reflected vigorous responses to I and C region differences, because rapid rejection through these regions was demonstrated using the PVG.r1 (AaIcCc) and PVG.r8 (AaIuCu) recombinants. The feeble immunogenicity of the Aa antigen for PVG animals was revealed by priming and cross-priming experiments showing not only that r1 failed to prime for subsequent r1 graft rejection, but that the Aa antigen presented in concert with Ia and Ca also failed to prime. An unexpected result was that the Aa antigen of r1 actually suppressed responsiveness, especially when delivered by a heart graft. This suppression not only extended to subsequent r1 grafts (for example, skin rafts) but also to subsequent grafts of a tissue. The mechanism of this suppression remains unclear but preliminary experiments argue in favor of enhancement rather than active suppression.

Animals↗

PubMed1985

Annual reproductive rhythms in mammals: mechanisms of light synchronization.

Animals restrict the time of birth of offspring to the most advantageous time of year, usually spring or summer. This is achieved by controlling the preceding period of fertility and, in some cases, by delaying implantation of the zygote. Seasonal changes in daylength, the principal, though not the only cue, regulate pulsatile release of hypothalamic releasing factors that in turn activates the pituitary-gonadal axis. The role of the neuroendocrine system is therefore to translate the photoperiodic stimulus into an endocrine signal (Figure 12). The measurement of day length is a function of the circadian system, environmental light being sampled on a 24-hour basis. Experimental manipulations of the photoperiodic response have revealed the existence of a rhythm of sensitivity to the presence of light that is entrained by the prevailing photoperiod. Light falling within the period of maximal sensitivity results in an LD type response. It is important to note that although different species measure day length in a similar manner, the gonadal response to a given photoperiod will vary between species depending upon the nature of their seasonal reproductive strategy. Photic information is conveyed from the retina to the pineal gland by way of the suprachiasmatic nuclei of the hypothalamus and the cervical sympathetic trunk. The central connections between these structures are poorly understood. The pineal is an essential mediator of the photoperiodic response. The effects of pinealectomy vary between species, but in all cases the responses to changes in day length are blocked. The gland is neither anti- nor progonadotrophic; it merely provides a signal. This signal is probably the nocturnal release of melatonin. Studies on in vivo melatonin production and the responses of photoperiodic species to timed administration of exogenous melatonin have suggested that the duration of nocturnal melatonin production by the pineal is read by the CNS as an indicator of the length of darkness. This model for PTM provides a physiological basis to the observed rhythm of sensitivity to light. This period of sensitivity is probably a parallel to the nocturnal rhythm of melatonin production. Light falling in this phase blocks melatonin production, truncates the pineal signal, and hence produces an LD response by the CNS. The site of the signal detector is not known, although the anterior hypothalamus may be involved. How the pineal signal triggers changes in the hypothalamic LHRH pulse generator is not known. The endogenous opioids, however, especially beta-END may have a major role in exercising photoperiodic control over pituitary action.

Animals↗

PubMed1985

Neurotoxic lesions of the anterior hypothalamus disrupt the photoperiodic but not the circadian system of the Syrian hamster.

This paper presents evidence which demonstrates that a site within the anterior hypothalamus of the Syrian hamster is essential for the expression of a photoperiodic response but not for the expression of oestrous or circadian activity rhythms. Selective lesions of the anterior hypothalamic nucleus (AHN) were produced by localized infusions of n-methyl aspartic acid (NMA). Histological analysis revealed that the suprachiasmatic and paraventricular nuclei were resistant to the toxin. Circadian locomotor activity rhythms and oestrous cyclicity were unaffected by these lesions but the photoperiodic response of the gonads to short day length (8L:16D) was completely prevented. In marked contrast to control animals, lesioned animals maintained large testes or ovulatory ovaries, even after 10 weeks of exposure to the inhibitory photoperiod. These data suggest that neurones within the AHN form an essential component of the photoperiod time-measuring apparatus which is independent of that controlling circadian rhythmicity.

Animals↗

PubMed1985

Changes in photoperiod alter the daily rhythms of pineal melatonin content and hypothalamic beta-endorphin content and the luteinizing hormone response to naloxone in the male Syrian hamster.

This study examines the possible involvement of beta-endorphin in the photoperiodic control of reproduction in the Syrian hamster. beta-Endorphin and LHRH concentrations in the medial basal hypothalamus (MBH), anterior hypothalamus (AHA), and the preoptic area (POA) as well as pineal melatonin content were determined by RIA in male Syrian hamsters exposed to either a long day [(LD) 16-h light; 8-h dark; lights on 0700-2300] or short day [(SD) 8-h light, 16-h dark; lights on 0700-1500] for 8 weeks. Groups of eight animals from each photoperiod were killed by decapitation at 4-h intervals over 24 h. Twenty minutes before death half the animals from each photoperiod were given naloxone (5 mg/kg, sc), the other half saline. Exposure to a long photoperiod maintained testicular activity while a short photoperiod induced testicular regression. Pineal melatonin content in both photoperiods was maximal at 0500 h, i.e. 2 h before the onset of light (SD, 435.58 +/- 82.7 pg/pineal; LD, 276.78 +/- 56.8 pg/pineal). However, the duration of the nighttime rise in pineal melatonin content was increased in SD animals with elevated melatonin levels at 2100 h (157.10 +/- 41.8 pg/pineal) and 0100 h (199.11 +/- 58.9 pg/pineal). In contrast pineal melatonin content in LD animals was only higher than daytime values at 0500 h. A daily rhythm of beta-endorphin content within both the AHA and MBH of animals exposed to a short photoperiod coincided with this prolonged nighttime rise in pineal melatonin content, although a causal relationship between the two was not established. Peak levels of beta-endorphin occurred at 2100 h (AHA, 6.569 +/- 1.2 pmol/mg protein; MBH, 4.877 +/- 0.45 pmol/mg protein) and at 0100 h (AHA, 6.107 +/- 0.66 pmol/mg protein; MBH, 4.49 +/- 00.79 pmol/mg protein) which was 6 h and 10 h into the dark phase, respectively, with lowest levels in the middle of the light phase (AHA, 3.561 +/- 0.56 pmol/mg protein; MBH, 2.688 +/- 0.3 pmol/mg protein). This rhythm was absent in animals exposed to a long photoperiod. There was no effect of photoperiod or time of day on the content of beta-endorphin in the POA. LHRH levels were not altered by changes in photoperiod in all three brain regions studied. In the AHA and MBH, concentrations of LHRH were similar at all times of day whereas, in the POA, LHRH levels varied with time in both photoperiods. Peak levels occurred in the middle of the dark phase at 0100 h (LD, 2.774 +/- 0.24 pmol LHRH/mg protein; SD, 3.206 +/- 0.48 pmol LHRH/mg protein) with lowest levels during the light phase (LD, 1.664 pmol LHRH/mg protein; SD, 1.775 pmol LHRH/mg protein).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗