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Biomedical subjects

J Herbert

Publications and source records attributed to J Herbert.

At least 163 records · Page 9Linked to original sources

The influence of steroid hormones on competing sexual and ingestive behavior in the male rat.

Water replete rats allowed restricted access to a sweet nonnutritive solution (0.2% Acesulfame-K) spend about one third of their time drinking it. This ingestive response is markedly inhibited if the male rat is simultaneously presented with an estrous female, but not an anestrous female or another male, despite the fact that there is sufficient time for both sexual and ingestive behaviors to occur. Castration and the subsequent decline in sexual behavior is accompanied by an increase in Acesulfame ingestion in the presence of a receptive female. Treatment with testosterone reverses both these effects. Similarly treatment of castrate males with DHT and estradiol (the active metabolites of testosterone) maintains both full sexual behavior and suppression of the ingestive response. However, the steroid requirements for sexual activity do not correspond completely with those for the sexually-induced suppression of ingestive behavior. Treatment of castrate males with estradiol alone maintains mounting behavior (but no intromissions or ejaculations) but does not suppress ingestive behavior in the presence of a receptive female--indeed under these suboptimal hormone conditions sexual behavior appears to be reduced in the presence of Acesulfame. Steroid hormones, therefore, have at least two effects upon sexual behavior. They enable certain aspects of sexual behavior such as intromissions and ejaculations, and also alter the animal's priority of response to two competing (ingestive and sexual) stimuli.

Animals↗

Intra-hypothalamic melatonin blocks photoperiodic responsiveness in the male Syrian hamster.

Exposure of male Syrian hamsters to a short daylength of 8L:16D leads to gonadal regression. This effect of photoperiod was prevented by pinealectomy or chronic exposure of the brain to exogenous melatonin delivered from in-dwelling cannulae. However, the effect of melatonin was dependent on the neural site of application. Melatonin delivered into the mid-brain, lateral hypothalamus or amygdala was ineffective. In contrast, bilateral administration of melatonin to the medial or amygdala was ineffective. In contrast, bilateral administration of melatonin to the medial hypothalamus prevented testicular regression and maintained high circulating levels of luteinizing hormone and prolactin. These findings suggest that the medial hypothalamus contains target sites for melatonin involved in pineal-mediated photoperiodic responses.

Animals↗

Nonidentical distribution of transferrin and ferric iron in human brain.

Using the avidin-biotin immunoperoxidase technique and a diaminobenzidine intensification of the Prussian Blue method, we have compared the distribution of transferrin to that of ferric iron in five normal autopsy brains from adult human males. The observed distribution of transferrin was considerably more widespread than: (1) that of histochemically demonstrable ferric iron; (2) that reported for transferrin in the fetal and neonatal human brain; and (3) that reported for transferrin in other species. Transferrin immunoreactivity was present in neurons, oligodendrocytes, astrocytes, ependymal cells, and choroid plexus epithelial cells, although not in all cells of any type. Ferric iron, on the other hand, was demonstrable only in oligodendrocytes, in myelin sheaths, and possibly in axons. While staining for both transferrin and iron was relatively high in the basal ganglia and substantia nigra, the pattern of staining differed, with striatal efferent fibers staining more heavily than the neuropil for iron and less heavily than the neuropil for transferrin. The choroid plexus, which in the rat has been shown to synthesize transferrin, stained heavily for transferrin and not at all for iron. The findings of low iron and high transferrin in the choroid plexus suggest that the plexus may secrete transferrin into the cerebrospinal fluid, thereby facilitating the translocation of iron within the neuraxis. Furthermore, the nonidentical distribution of ferric iron and transferrin suggests that, in the human brain, transferrin may serve other functions besides the transport of iron from extracellular fluid to cytoplasm.

Adult↗

The effects of simultaneous or separate infusions of some pro-opiomelanocortin-derived peptides (beta-endorphin, melanocyte stimulating hormone, and corticotrophin-like intermediate polypeptide) and their acetylated derivatives upon sexual and ingestive behaviour of male rats.

Intraneuronal post-translational cleavage of pro-opiomelanocortin yields a variety of peptides including beta-endorphin, melanocyte stimulating hormone and corticotrophin-like intermediate polypeptide, some of which are subsequently N-acetylated. Such peptides may be co-released from neuronal terminals, and so these experiments explored the effects of co-administration of some of them on sexual behaviour in the male rat, which is known to be sensitive to hypothalamic infusions of beta-endorphin. Peptides were infused into the pre-optic-anterior hypothalamic area bilaterally in doses up to 320 pmol, and males allowed access to a sexually receptive female and/or a sweet solution (0.1% Acesulfame-K) for 15 min, so that both sexual and ingestive behaviour could be studied. beta-Endorphin(1-31) by itself inhibited sexual interaction, confirming our previous data. Acesulfame-K ingestion was inhibited in control-infused rats in the presence of a female, but this inhibition was released when sexual behaviour was itself diminished by beta-endorphin(1-31). Both the acetylated and non-acetylated forms of melanocyte stimulating hormone (alpha-melanocyte stimulating hormone and des-acetyl melanocyte stimulating hormone) stimulate sexual behaviour; latencies both to ejaculation and to resumption of copulatory behaviour after an ejaculation (post-ejaculatory interval) were reduced. However, infusion of either corticotrophin-like intermediate peptide or N-acetylated beta-endorphin (1-31) had no effect on either sexual or ingestive behaviour. Infusion of either acetylated melanocyte stimulating hormone or des-acetyl melanocyte stimulating hormone mixed with beta-endorphin(1-31) prevented the inhibitory effect of the latter on sexual behaviour. Dose-response studies showed that the behavioural effect of such mixtures depended upon the molar ratios of the two peptides, rather than their absolute concentrations. The higher the ratio in favour of alpha-melanocyte stimulating hormone or des-acetyl melanocyte stimulating hormone, the greater the display of sexual behaviour. Infusing either corticotrophin-like intermediate polypeptides or N-acetyl beta-endorphin(1-31) with beta-endorphin(1-31) did not prevent the inhibition of sexual activity expected with beta-endorphin(1-31) alone. These results are discussed in terms of the functional consequences of co-release of proopiomelanocortin peptides from hypothalamic nerve terminals.

Acetylation↗

Expression of the insulin-like growth factor II gene in the choroid plexus and the leptomeninges of the adult rat central nervous system.

The rat insulin-like growth factor II gene, encoding a fetal somatomedin, expresses a multitranscript family in embryonic/fetal tissues and in the adult brain and spinal cord. By performing in situ hybridization on tissue sections of adult brain and spinal cord, we have found that these transcripts are not expressed in neural or glial cells but are expressed in the epithelium of the choroid plexus of each cerebral ventricle and in the leptomeninges. We propose that the choroidal epithelial cells synthesize and secrete insulin-like growth factor II into the cerebrospinal fluid.

Animals↗

Strategies of monoclonal antibody therapy that induce permanent tolerance of organ transplants.

Treatment of normal rats with certain monoclonal anti-CD4 antibodies, beginning on the day of grafting, prevents heart graft rejection across a full MHC-haplotype mismatch. Adequate doses of antibody MRC OX-35, which is very potent in vivo, led to the induction of authentic specific tolerance of the transplants. In the very stringent grafting test of transplantation of DA skin to high-responder LOU recipients, adjunctive therapy with cyclosporine, in addition to the anti-CD4 antibodies, is required to induce tolerance. Since tolerance persists indefinitely after a 30-day course of treatment and appears to involve T cell-mediated suppression, this form of treatment is of potential clinical interest.

Animals↗

Pattern of the insulin-like growth factor II gene expression during rat embryogenesis.

The rat insulin-like growth factor II (IGF-II) gene, encoding a fetal somatomedin, expresses a family of transcripts in embryonic/fetal tissues, and also in the adult choroid plexus and the leptomeninges. We have localized IGF-II gene transcripts in sections of rat embryos of embryonic days 10-16 by performing in situ hybridization. These transcripts are present in the head mesenchyme, formed from both the mesoderm and the cephalic portion of the neural crest, and also in the majority of other tissues of mesodermal origin, predominantly those derived from the somites and the lateral mesoderm. Intense labelling was detected in muscle cells, and their precursors, throughout the examined stages, whereas in chondrocytes the initial high level of hybridization declined substantially prior to ossification. IGF-II gene transcripts are also present in derivatives of other germ layers, but in restricted sites. Thus, from the derivatives of the endoderm, only the liver and the bronchial epithelium yielded hybridization signals. Ectoderm-derived tissues, including the central and peripheral nervous system, were negative for hybridization, with the exception of the choroid plexus, the newly forming pituitary rudiment and, to a lesser extent, the auditory placode. The pattern of IGF-II gene expression during embryogenesis overlaps significantly with the reported distribution of immunohistochemically detected TGF-beta 1. A paracrine/autocrine role for IGF-II in the developmental process is discussed.

Animals↗

The expression of viral and cellular genes in papillomas of the choroid plexus induced in transgenic mice.

A line of transgenic mice that carry the SV40 gene for the large Tumor antigen express this protein during the first two weeks of life in brain tissue. By 30-40 days after birth, independently derived multiple foci of abnormal cells appear throughout the choroid plexus. After 90 days, higher levels of T antigen and rapid tumor growth are detected and all these animals die in a narrow time span, between 100-120 days. In situ hybridization with tissue sections and Northern blot analysis have been employed to follow the steady state levels of SV40 RNA and the p53 oncogene RNA levels in normal and tumor tissues. The level of SV40 RNA is quite variable between tumor cells in a section. This heterogeneity of T antigen mRNA levels could permit the selection of cells (from the multiple foci) expressing higher levels of T antigen and growing more rapidly. The increased levels of p53 RNA observed in tumor cells could then result from the active growth state of these cells or a more direct transcriptional activation. Two cellular genes, transthyretin and the 5-HT1C serotonin receptor, both of which are preferentially expressed in normal choroid plexus cells, were also examined for RNA production in these tumors of the choroid plexus. Both of these genes produced high levels of RNA in tumor tissue indicating the retention of well differentiated gene expression in these tumor tissues. This reflects, at the level of gene expression, the well differentiated morphology of these papillomas of the choroid plexus. Interestingly, as cell lines have been derived from these tumors, both the choroid plexus specific RNA species (for 5-HT1C receptor) and characteristic morphology were lost and an increase in T antigen levels was observed.

Animals↗

Isolation and characterisation of goat C-reactive protein.

A pentraxin was isolated from acute phase goat serum by its calcium-dependent affinity for agarose, and although it did not bind to phosphorylcholine immobilised on Sepharose, its binding to agarose was reversed by exposure to fluid phase phosphorylcholine. It was identified as goat C-reactive protein on the basis of its immunochemical cross-reactivity with human and bovine C-reactive protein. The molecule was composed of five identical, glycosylated, non-covalently associated subunits, each of molecular weight approx. 24,000. Acute phase serum levels in a small number of samples were not significantly different from normal levels (means 72 and 55 micrograms/ml, respectively), suggesting that goat C-reactive protein is not a major acute phase reactant. No other pentraxin was detected in goat serum.

Animals↗

Safe anesthesia for endoscopic laryngeal laser surgery.

Anesthesia safety for endoscopic laryngeal laser surgery has been a major limiting factor for laser applications in the larynx and the hypopharynx. Several anesthesia techniques have been proposed and each technique appears to have its own limitations. This paper will deal with the distinct advantages offered by the malleable copper tube which is used for delivery of the open Venturi system anesthesia for endoscopic laser surgery. A retrospective study of 100 patients who have undergone this modality of anesthesia at our institution will be presented. Our conclusion from this study shows clearly the superiority of the copper tube over the conventional aluminium-foil-wrapped endotracheal tube in safety and the exposure of the larynx during surgery.

Anesthesia↗

Selective effects of beta-endorphin infused into the hypothalamus, preoptic area and bed nucleus of the stria terminalis on the sexual and ingestive behaviour of male rats.

beta-Endorphin was infused bilaterally into the medial preoptic area-anterior hypothalamic continuum at doses of 5, 10 and 40 pmol each side. The highest dose selectively abolished mounting, intromitting and ejaculating in sexually experienced male rats paired with an oestrous female. Males infused with 40 pmol beta-endorphin still followed the female, investigated her anogenital region and other parts of her body, but made abortive attempts to mount. A dose of 5 pmol beta-endorphin had no effect, but 10 pmol proved partially effective. The same males, in other tests, were allowed to ingest a highly preferred, sweet, non-calorific solution (acesulfame-K) in the absence of a female. beta-Endorphin infusions (up to 40 pmol) into the same area of the hypothalamus had no effect on this behaviour. Control males allowed simultaneous access both to an oestrous female and to the sweet solution copulated normally but reduced their ingestive behaviour, despite there being sufficient time during tests for both to occur. beta-Endorphin (40 pmol) infused into the preoptic area-anterior hypothalamic continuum under these conditions suppressed sexual interaction, but ingestion of acesulfame-K increased to values observed when the female was absent. beta-Endorphin infused into neighbouring areas of the brain had different behavioural effects. Sexual behaviour was not inhibited, and ingestion of acesulfame-K was unaltered, when beta-endorphin was infused either into the bed nucleus of the stria terminalis or the rostral ventromedial hypothalamus. However, infusions of cholecystokinin-8 into the ventromedial hypothalamus suppressed acesulfame-K ingestion in most animals, showing that the cannulae were placed in an area regulating ingestive behaviour. The inhibition of sexual behaviour after preoptic area-anterior hypothalamic continuum infusions of beta-endorphin was prevented by either pretreating rats with 1 mg/kg naloxone intraperitoneally, or by infusing a putative delta opiate receptor blocker (0.5 pmols ICI 174864) into the preoptic area-anterior hypothalamic continuum 5 min prior to beta-endorphin treatment. ICI 174864 administered alone significantly increased mount rate and reduced the post-ejaculatory refractory period in copulating males. These experiments suggest that there is both neurochemical and neuroanatomical specificity relating beta-endorphin to sexual behaviour in the male rat.

Animals↗

The effects of castration, testosterone replacement and photoperiod upon hypothalamic beta-endorphin levels in the male Syrian hamster.

Syrian hamsters kept in long day-lengths have active gonads and high circulating levels of gonadal steroids. Under the influence of the pineal gland, animals exposed to short photoperiods undergo testicular regression, have low circulating levels of testosterone and gonadotrophins and elevated levels of beta-endorphin within the hypothalamus. This paper describes the interaction between testosterone and photoperiod in the regulation of beta-endorphin levels in three regions of the hypothalamus. Hypothalamic beta-endorphin levels were measured by a combination of high-performance liquid chromatography and radioimmunoassay techniques that allows separation of the beta-endorphin (1-31) peptide from its metabolites and precursors. All of the beta-endorphin-like immunoreactivity in the hypothalamus of the male hamster, in both photoinhibited and photostimulated conditions, was found to represent the 31-amino-acid peptide. In photostimulated hamsters, chronic castration was associated with a significant increase of beta-endorphin levels in the anterior hypothalamus and mediobasal hypothalamus, which was reversed by treatment with exogenous testosterone. Castration prevented the ability of naloxone, an opiate receptor antagonist, to release luteinizing hormone, and this effect was also reversed by exogenous steroid. In photoinhibited hamsters, however, castration had no effect upon beta-endorphin levels in the preoptic area or mediobasal hypothalamus, and there was only a small increment in the anterior hypothalamus. Significantly, beta-endorphin levels in all areas of the hypothalamus of photoinhibited castrates were not decreased by testosterone treatment. In addition, administration of exogenous testosterone did not restore sensitivity to naloxone in these animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Isolation of a cDNA clone encoding subunit IV of human cytochrome c oxidase.

We have isolated a full-length human liver cDNA clone specifying the nuclear-encoded subunit IV of the human mitochondrial respiratory chain enzyme, cytochrome c oxidase (COX; EC 1.9.3.1). The human cDNA clone is highly homologous to its bovine counterpart in the coding regions for both the mature polypeptide and the presequence, and the gene is evolving more slowly than that of any of the three mitochondrially encoded COX subunit genes. We find no preliminary evidence for tissue-specific isoforms of COX subunit IV, as Northern analysis of muscle, liver, and HeLa cell RNA shows an identically sized transcript in each cell type.

Amino Acid Sequence↗

Lymphocyte subpopulations and memory of MHC antigens. I. Quantitative aspects of neonatal heart graft rejection in normal and immune rats.

Using PVG-RT1av1 neonatal heart grafts transplanted to the plantar space in irradiated PVG recipients, and adoptive transfer of normal and immune cells, we have analyzed the role of lymphocyte subsets in graft rejection. This assay was found to be reproducible and to show good dose-response characteristics, permitting a precise analysis of the potency of the cells transferred. Immune cells were 36 times more potent than normal cells and all of their activity was in the T cell fraction. The increase in potency of immune populations was entirely within the CD8+ population defined by the mouse monoclonal antibody MRC OX-8. The CD4+ population, defined by the antibody W3/25, in both normal and immune populations, restored first-set rejection. All the graft rejection activity of CD4+ cells could be ascribed to the MRC OX-22- subset of these cells.

Animals↗

Effect of asymmetrical reductions of photoperiod on pineal melatonin, locomotor activity and gonadal condition of male Syrian hamsters.

This study investigated the relationship of two overt circadian rhythms, locomotor activity and melatonin synthesis in the pineal gland, by comparing their responses to asymmetrical reductions in photoperiod. Transfer of male Syrian hamsters from long to short daylengths led to an increase in the duration of both locomotor activity and the period of melatonin synthesis. Over the course of re-entrainment, the two rhythms were held in a stable phase relationship, and the direction of the switch did not influence the rate of decompression or the final phase relationships established after 8 weeks in short daylengths. Decompression of the activity rhythm was not influenced by pinealectomy. Exposure to short photoperiods caused gonadal regression and a consequent decline in serum testosterone levels from 10 to less than 1 nmol/l. The direction of the photoperiodic switch did not affect the time-course of gonadal regression. These data demonstrate the important influence of photoperiod upon the duration of the nocturnal peak of melatonin production by the pineal and also demonstrate that this effect is one example of a more widespread response of the circadian system. A qualitatively similar signal controls both locomotor activity and melatonin synthesis, although the neural basis of this common mechanism is unclear.

Animals↗

Relation between aggressive behaviour and circadian rhythms in cortisol and testosterone in social groups of talapoin monkeys.

Circadian rhythms in cortisol and testosterone in both blood and cerebrospinal fluid (CSF) were studied in four groups of male and female talapoin monkeys. Samples were taken 4 h apart under two conditions: whilst the sexes were kept separate (isosexual) and again after 24 h of interaction (heterosexual). There were similar rhythms in cortisol in males and females during the isosexual condition, though in blood (but not in CSF) mean levels were higher in females. Heterosexual interaction increased cortisol levels in both sexes (though more so in males), and also altered the shape of the rhythm, acrophase being delayed by 4 h in males and by 2 h in females. The amplitude of the rhythm was not altered. Cortisol levels were positively correlated in both males and females with the amount of aggression received from other males, but not from females nor with the animal's social rank. Circadian rhythms in serum testosterone in males were also altered by heterosexual interaction. Access to females delayed acrophase by 2 h, but had no effect on mean levels (unlike the effect on cortisol). As for cortisol, the amplitude of the testosterone rhythm remained unchanged. Serum testosterone was negatively correlated with aggression from males, but not from females nor with sexual interaction. This was associated with a pronounced decrease in the levels of testosterone during the night, not observed in males receiving no aggression from others. There was a non-significant trend towards a positive correlation between social rank and serum testosterone.(ABSTRACT TRUNCATED AT 250 WORDS)

Aggression↗