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Biomedical subjects

J Herbert

Publications and source records attributed to J Herbert.

At least 19 recordsLinked to original sources
PubMed1992

Differential effects of excitotoxic basolateral and corticomedial lesions of the amygdala on the behavioural and endocrine responses to either sexual or aggression-promoting stimuli in the male rat.

The effects of discrete excitotoxic lesions of the basolateral (BL) and corticomedial (CM) amygdaloid areas on both male rat sexual behaviour and inter-male agonistic behaviour were investigated. The effects of the same lesions on the hormonal responses (luteinising hormone (LH) following sexual behaviour, corticosterone following aggressive interactions) which accompany these behavioural responses were measured. Basolateral lesions had no effect on male sexual behaviour but significantly reduced the level of aggressive inter-male behaviour. However, the increase in plasma corticosterone concentration which occurs after such an interaction was not affected by basolateral lesions. In contrast, corticomedial lesions did not affect inter-male offence but severely affected copulatory behaviour, including a significant decrease in the males' investigation of the receptive female. However, the increase in plasma LH concentrations induced by the presence of a receptive female was not affected by the CM lesion. These results demonstrate a dissociation between the two amygdaloid regions with respect to the contributions made to the two social behaviours under study. This anatomical division may reflect differential amygdaloid sensory control of these behaviours. A further dissociation between amygdaloid contribution to behavioural and hormonal responses was also revealed. Neither hormonal response showed a parallel decline with the relevant behavioural response, suggesting that neither the basolateral nor corticomedial amygdaloid complex is responsible for coordinating behavioural and endocrine responses to a specific stimulus.

Agonistic Behavior↗
PubMed1992

Specific effects of beta-endorphin infused into the amygdala on sexual behaviour in the male rat.

Bilateral intra-amygdaloid infusions of 0, 20, 60, 120 and 200 pmol beta-endorphin were administered to sexually experienced male rats in a Latin-square design. Sixty, 120 and 200 pmol beta-endorphin significantly decreased preintromission investigation rate and increased intromission latency with an oestrous female. No other effects on the male rats' sexual behaviour were produced. beta-Endorphin-induced effects on preintromission investigation and intromission latency were naloxone reversible (5 mg/kg, i.p.). Similar doses of intra-amygdaloid beta-endorphin had no effect on aggressive interaction with another, strange, male behaviour and similar doses of intra-amygdaloid corticotropin-releasing factor had no effect on sexual behaviour. Thus, there was both behavioural and chemical specificity of intra-amygdaloid beta-endorphin-induced effects on male sexual behaviour. Bilateral 60 pmol beta-endorphin infusions into the caudate-putamen had no effects on male sexual behaviour, demonstrating anatomical specificity of the intra-amygdaloid-induced effects. Basolateral excitotoxic lesions did not prevent the behavioural effects of intra-amygdaloid beta-endorphin infusions. These results demonstrate that intra-amygdaloid beta-endorphin specifically suppresses the precopulatory phase of male rat sexual behaviour but leaves the execution of the copulatory series intact once it has been initiated. This effect appears to be mediated via the corticomedial amygdaloid region. The change in precopulatory behaviour suggests that beta-endorphin may interfere with the processing of sensory information from the female, thus delaying appropriate initiation of the copulatory series.

Aggression↗
PubMed1992

The effects of beta-endorphin infusions into the amygdala on visual and olfactory sensory processing during sexual behaviour in the male rat.

Sexually experienced male rats infused bilaterally into the amygdala with 60 pmol beta-endorphin show decreased rate of precopulatory investigation of the female and delayed intromission latency, but copulation is left unaltered. Such males are still able to discriminate between the odours of bedding from receptive and unreceptive females, demonstrating that beta-endorphin does not impair the ability to detect sexually relevant odours. Preventing visual cues emitted by females during proceptive behaviour (by treating them with haloperidol) delayed intromission latency but had no effect on preintromission investigation. Intra-amygdaloid beta-endorphin exacerbated the effects of this treatment on the intromission latency. Inducing anosmia in males (by applying zinc sulphate solution to the olfactory mucosa) decreased their anogenital investigation and delayed their intromission latency. These effects were not enhanced by intra-amygdaloid beta-endorphin. Allowing males to investigate and initiate the first intromission prior to intra-amygdaloid infusion had no effects on subsequent intromissions. However, if following an intromission with one female and an infusion of beta-endorphin, the male was presented with an unfamiliar female then the effects of intra-amygdaloid beta-endorphin on investigation and intromission returned. These results suggest that beta-endorphin in the amygdala interferes with the processing of female-specific olfactory information. Without this processed information, classification of the female as a sexual stimulus may be impeded and thus sexual arousal delayed.

Amygdala↗
PubMed1992

Expression of c-fos in regions of the basal limbic forebrain following intracerebroventricular corticotropin-releasing factor in unstressed or stressed male rats.

Corticotropin-releasing factor has an integrative role on the behavioral, endocrine and autonomic responses to stress. Immediate-early gene (c-fos) expression was used to determine patterns of neural activity in the limbic system following i.c.v. infusion of corticotropin-releasing factor. Either 250 or 1000 pmol corticotropin-releasing factor infused into the lateral ventricle of precannulated and handled male rats resulted in marked c-fos expression 60 or 120 min later in localized regions of the basal forebrain, including the ventrolateral septum, the dorsal and medial parvicellular divisions of the paraventricular nucleus, the central nucleus of the amygdala, and dorsal bed nucleus of the stria terminalis. Pre-infusion of alpha-helical corticotropin-releasing factor (2500 pmol), a competitive corticotropin-releasing factor antagonist of corticotropin-releasing factor, had no effect on immediate-early gene expression alone but reduced that elicited by exogenous i.c.v. corticotropin-releasing factor (250 pmol)--in some areas to control levels. Fifteen minutes of restraint stress, a situation in which corticotropin-releasing factor is released endogenously, also activated c-fos expression in a pattern that resembled corticotropin-releasing factor infusions but was not identical. There was enhanced expression in the dorsal and medial areas of the paraventricular nucleus, but not its magnocellular region, and increased expression in the ventrolateral septum; however, there was no detectable response on the central amygdala. Preinfusion of alpha-helical corticotropin-releasing factor (2500 pmol) had no significant effect on stress-induced c-fos expression in the ventrolateral septum or paraventricular nucleus. This suggests that corticotropin-releasing factor release may form only a part of the central neurochemical response to restraint stress. Rats given i.c.v. corticotropin-releasing factor (250 pmol) before restraint stress showed additive effects on c-fos in the ventrolateral septum but not in the paraventricular nucleus; the central nucleus of the amygdala reacted as if corticotropin-releasing factor alone had been infused. Corticosterone levels were raised by both stress and corticotropin-releasing factor, but pretreatment with alpha-helical corticotropin-releasing factor reduced them after either procedure, which correlates with c-fos expression in the paraventricular nucleus and ventrolateral septum. These results show that corticotropin-releasing factor induces a specific pattern of c-fos expression in localized regions of the amygdala, hypothalamus and septum, which may indicate a corresponding pattern of neural activation. Restraint, one form of stress, activates c-fos in a similar but not identical manner, suggesting that corticotropin-releasing factor may not be the only neuropeptide involved in the response to this stressor.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Regional expression of c-fos antigen in the basal forebrain following intraventricular infusions of angiotensin and its modulation by drinking either water or saline.

The expression of c-fos protein was examined in the basal forebrains of male rats 60 min following intracerebroventricular infusions of 250 pmol angiotensin II. Levels of corticosterone and vasopressin were also measured at the same time point. In animals not allowed access to water after infusion, angiotensin II induced intense c-fos expression in a band of neurons extending throughout the anterior region of the third ventricle region, including the organum vasculosum of the lamina terminalis, the median preoptic nucleus (nucleus medianus) and the subfornical organ. There were also high levels of expression in the hypothalamic supraoptic nucleus and the paraventricular nucleus, particularly its lateral (magnocellular) region, though other, parvicellular areas were also affected. No other area of the hypothalamus was altered. There was increased c-fos expression in the central nucleus of the amygdala and the bed nucleus of the stria terminalis. Allowing rats to drink during the 60-min survival period modified this pattern of response. c-fos was markedly reduced in the supraoptic nucleus and the paraventricular nucleus but not in the other areas examined, including the anterior region of the third ventricle and the amygdala. When water was withheld for 15 min, but then allowed, rats drank the same total volume but c-fos expression was no longer inhibited in either the supraoptic nucleus or paraventricular nucleus. When rats were given 0.9% saline to drink, they ingested about three times as much as water, but angiotensin II-induced c-fos expression was similar to that in rats denied access to water. The pattern was similar following access to 1.8% saline, though levels in the organum vasculosum of the lamina terminalis were reduced. There was a marked correlation between the number of c-fos-positive neurons in the supraoptic nucleus or paraventricular nucleus and plasma levels of corticosterone 60 min after infusion, but not with arginine-vasopressin levels. These experiments show that angiotensin II induces highly localized expression of c-fos in areas known to be concerned with the dipsogenic and endocrine actions of this peptide, and that this pattern is selectively altered by allowing the animal to drink solutions of different tonicity. Immediate-early gene expression is a novel and valuable method of determining the neural response to peptides at the cellular level.

Angiotensin II↗
PubMed1992

Familial amyloidotic polyneuropathy presenting with carpal tunnel syndrome and a new transthyretin mutation, asparagine 70.

We report familial amyloidotic polyneuropathy in a pedigree of German ancestry residing in New Jersey. Eight affected subjects presented in the third to seventh decade with carpal tunnel syndrome (CTS) and one subject presented with vitreous opacification. Transmission was autosomal dominant and survival was prolonged. Affected subjects were heterozygous for a novel mutation in serum transthyretin (TTR), resulting in an asparagine for lysine substitution at residue 70 of the TTR monomer. We report two methods for rapid identification of the mutation based on the polymerase chain reaction. This pedigree further emphasizes the evolving phenotypic and genotypic heterogeneity of the transthyretinopathies. Familial or sporadic CTS or unexplained vitreous opacification suggest the possibility of TTR amyloidosis and should prompt a search for TTR mutations.

Adult↗
PubMed1992

A nonphotic stimulus causes instantaneous phase advances of the light-entrainable circadian oscillator of the Syrian hamster but does not induce the expression of c-fos in the suprachiasmatic nuclei.

The study investigated whether nonphotic cues that alter the phase of overt circadian rhythms do so by causing instantaneous shifts in the underlying, light-sensitive clock. Wheel-running activity in Syrian hamsters was studied under free-running conditions of constant dim red light as an overt marker of circadian phase, the daily onset of activity being defined as circadian time 12 (CT 12). Exposure to a 15 min pulse of bright light at CT 12.20 caused a phase delay in activity onset, whereas pulses delivered at CT 11.20 had no effect upon the overt rhythm. Correlated with their effect on behavior, light pulses delivered at CT 12.20 induced expression of c-fos-like immunoreactivity in the retinorecipient regions of the suprachiasmatic nuclei of the hypothalamus (SCN), whereas pulses delivered at CT 11.20 had no effect upon the expression of c-fos. Expression of this immediate-early gene therefore provided a second marker of circadian phase, because its induction by light is closely correlated with the onset of subjective night (CT 12). To establish a suitable protocol for nonphotic shifts of the activity rhythm, animals were handled and received a subcutaneous injection of saline at different circadian phases. Injections at CT 8 or CT10 caused an immediate bout of wheel-running activity, and a consequent phase advance in the activity rhythm as assessed by the earlier onsets of activity in successive days. Handling and injections at other circadian phases were without effect. Despite shifting the overt rhythm, these procedures at CT 10 did not lead to the expression of c-fos in the SCN.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Temporal expression of the transthyretin gene in the developing rat eye.

Transthyretin (TTR) is a 55-kilodalton tetrameric protein that plays an important role in the plasma transport of thyroxine and retinol. Plasma TTR is synthesized in the liver, but major sites of synthesis also have been described in the choroid plexus (CP) epithelium, the visceral yolk sac, and the eye. Recently, the retinal pigment epithelium (RPE) was identified as the specific site of TTR synthesis in the rat eye, and it was suggested that this established a functional homology between the RPE and the CP epithelium. In this study, the temporal pattern of TTR mRNA expression was investigated in the rat eye and brain during development (embryonic day 10 [e10]-postnatal day 7 [P7]) by in situ hybridization and quantitative densitometry. The TTR mRNA was present in abundance in the primordial CP before organogenesis (e10-12), but in the eye, TTR mRNA first was detected at considerably lower levels after organogenesis (e16) and only in a subset of RPE cells in the equatorial region. The relative abundance of TTR mRNA in RPE rose gradually until e21, but on the first day of life a surge was seen, followed by stabilization at adult levels by P7. These findings suggest that the requirement for TTR in CP and RPE, and possibly its function, may differ during development. The postnatal surge in RPE TTR message levels raises the possibility that transcription of the TTR gene in the newborn animal may be responsive to newly encountered environmental stimuli in the perinatal period, such as incident light.

Animals↗
PubMed1991

Preventing cystic fibrosis in the RSA.

Prenatal diagnostic testing for cystic fibrosis (CF) in South Africa has been available by microvillar enzyme (MVE) assay since 1984 and by DNA investigation since 1987. The advantages and practical uses of these two procedures are reviewed. Over the period 1984-1989, 59 MVE assays and 13 DNA investigations (1 woman had both done; total number of pregnancies tested 71) were performed for the prenatal diagnosis of CF in high-risk families. Of the 71 pregnancies tested (65 white woman, 4 mixed race and 2 Indian), 18 fetuses were found to be affected: of these, 15 couples chose to have the pregnancies terminated. In 2 fetuses tested the MVE assays were 'equivocal' and the babies were born affected. By using population genetic and demographic data it is estimated that the present rate of prenatal diagnosis and prevention satisfies about one-quarter of the projected and practically achievable annual need. It is also tentatively shown that only about 60% of the projected number of high-risk families are at present on record. It is concluded that more systematic efforts should be directed at carefully guided information and awareness campaigns, in order to draw more CF families into the mainstream of voluntary genetic services. The identification and cloning of the CF gene (in 1989) has made it possible to extend considerably the present strategy of prevention and to include lower-risk and extended CF families in due time.

Amniotic Fluid↗
PubMed1991

Cortisol hypersecretion in depressed school-aged children and adolescents.

A prospective longitudinal study has been carried out to determine the secretory pattern of cortisol in children (n = 10) with major depressive disorder. Salivary cortisol samples were collected at 4-hourly intervals over 24 hours when the subjects were depressed and again when they were recovered. Group comparison indicated that significant increases in mean cortisol output occurred during illness as compared with recovery. This difference occurred only at three points (midnight, 4 a.m., 8 a.m.) of six measured. Not all cases were showed hypersecretion, but when hypersecretion was present, it occurred in cases with more severe symptoms. In addition, marked differences existed within individuals in the depressed state vs. the recovered state. Hypersecretion appeared to be associated with a significant alteration in diurnal rhythm in some, but not all, cases. The degree of cortisol responsivity and the shape of the curve over 24 hours during the depressed state deserve further investigation and may have implications for the course and outcome of major depression in this age group.

Adolescent↗
PubMed1991

Brain aromatization of testosterone in the male Syrian hamster: effects of androgen and photoperiod.

Estrogen formed by aromatization of testosterone (T) is involved in the activation of sexual behavior and control of the neuroendocrine system in the male Syrian hamster. Our study examined whether daylength influences formation of estrogen in the preoptic area (POA) and other neuroendocrine areas (anterior hypothalamus, AHT, and medial amygdala, MA) which are targets for T in behaviorally active males. Estrogen formation in individual brain samples was assayed in vitro using the stereospecific production of 3H2O from (1 beta-3H) T as a measurement of aromatase activity. Serum levels of PRL, LH, FSH and T were compared with brain aromatase activity. Groups of intact, castrated and T-treated (chronic silastic T implants) male hamsters, previously selected on behavioral criteria as being sexually active, were maintained on long (16:8LD) or short (8:16LD) daylength for 16 weeks. Two further groups of males either intact or castrated and T-treated were shifted after 7 weeks from the long photoperiod to 12:12LD. POA, AHT and MA areas of sexually active males contained active aromatase systems which converted 3H-T to estrogens. Enzyme activity differed between the areas (POA, MA greater than AHT). Aromatase activity was low in medial septum and cerebral samples. Castration, which reduced serum T to undetectable levels and elevated LH and FSH, had no effect on preoptic aromatase activity. Although estrogen formation in POA did not differ between 8:16LD and 16:8LD males, castration reduced aromatase activity in AHT of both short- and long-day groups. Aromatase activity in AHT was also significantly reduced in photo-inhibited 12:12LD intact males. There was no analogous decrease in 5 alpha-reductase or 17 beta-hydroxysteroid dehydrogenase (HSD) activity, indicating a specific effect on the aromatase. The effect of photoperiod on aromatase activity was not reversed by T treatment. Therefore, photoinhibition acts in part through the effects of reduced T levels on the anterior hypothalamus, but it also acts independently of circulating T. Our results suggest that both androgen and photoperiod may regulate the AHT aromatase system and that this occurs by different mechanisms. The more active aromatase system in POA is insensitive to both castration and photoperiod. Behavioral deficits in short-day males are not due to changes in the preoptic aromatase system, but may be related to changes in aromatase activity within AHT. We conclude that there is a difference in the regulation of two locally active aromatase systems within the preoptic-anterior hypothalamic complex of the male hamster.

Animals↗
PubMed1991

[The symptomatic therapy of cervical hard-substance defects with dentin-adhesive-composite systems].

For covering of hypersensitive, morphologically disturbed and non-esthetic cervical (wedge-shaped) defects of hard dental tissues, dentine adhesive composite systems are suitable for a careful and less invasive preparation. Presumption is a smooth and at probing hard-touched defect surface. A clinical 2 year study (15 patients with 143 cervical lesions) using 5 different dentine adhesive composite systems resulted in superiority of the hybrid composite P-30 in view of low filling losses (after 1 year: 1 of 28 fillings after 2 years: 2 of 27 fillings), the acceptable bond zone morphology (after 1 and 2 years clinical intact bond zones), and a constant volume behaviour (after 1 and 2 years no clinical changes of volume). The micromorphological evaluation correlated in a lot of cases with the clinical findings after 2 years. It has to be expected that improved dentine adhesive composite systems together with changed setting mechanisms of dentine adhesives will be able to eliminate filling losses in the treated indication.

Composite Resins↗
PubMed1991

The distribution of retinol-binding protein and its mRNA in the rat eye.

Although a constant supply of retinol is a critical requirement for the visual cycle, the molecular mechanisms underlying retinol delivery, uptake, storage, and transport in the eye are not well understood. Previously the synthesis of serum retinol-binding protein (RBP) in the mammalian eye was reported. Now the distribution of RBP and RBP mRNA in the rat eye has been studied by immunohistochemical and in situ hybridization techniques has been studied. The RBP mRNA was present only in the cytoplasm of retinal pigment epithelial (RPE) cells, terminating abruptly at the pars plana. On the other hand, RBP immunoreactivity was more widespread. The most intense immunostaining was present in retinal ganglion cells, the corneal endothelium, and under certain conditions of tissue fixation, the corneal epithelium. Consistent but less intense immunoreactivity was detected in the photoreceptors, Müller cells, inner plexiform layer, ciliary epithelium and stroma, iris epithelium, retinal pigment epithelium, lacrimal glandular epithelium, and periorbital soft tissues. These findings suggest that RBP synthesized by the RPE may be secreted to various ocular locations. However, at present, uptake from plasma cannot be excluded as another possible source of ocular RBP. In the plasma, holo-RBP (the retinol-RBP complex) is transported in complex with another plasma protein, transthyretin (TTR). This substance is also synthesized by the RPE and its distribution in the eye is similar to that described for RBP. Taken together, these findings support the proposal that ocular RBP and TTR may function cooperatively in the intraocular translocation of retinol.

Animals↗
PubMed1990

The retinal pigment epithelium is the unique site of transthyretin synthesis in the rat eye.

Transthyretin (TTR), or prealbumin, is a 55-kD tetrameric protein which plays an important role in the plasma transport of thyroxine, and through its interaction with retinol-binding protein, of retinol. Four major sources of TTR synthesis have been identified in the mammal: liver hepatocytes, visceral yolk sac endoderm, choroid plexus epithelium, and the eye. We now report in situ hybridization studies demonstrating that in the rat eye, the retinal pigment epithelium is the unique source of TTR synthesis. This finding underscores the developmental, structural, and functional homology between the choroid plexus epithelium and the retinal pigment epithelium. Although the functional significance of ocular TTR synthesis is unclear, it is likely that it serves to transport thyroxine or retinol across the blood-retina barrier, thereby facilitating their effects on differentiation and morphogenesis. Considering the importance of retinol in the biochemistry of the visual process, we propose that TTR may play a role in the intraocular cycling of retinol.

Animals↗
PubMed1979

The effects of different photoperiods on circadian 5-HT rhythms in regional brain areas and their modulation by pinealectomy, melatonin and oestradiol.

Differential circadian rhythms in 5-HT levels were found in the hypothalamus and pineal (but not in the cortex, hippocampus or midbrain) in ferrets kept in either long (14 h light/10 h dark) or short (8 h light/16 h dark) photoperiods. 5-HT decreased during the first 6 h of illumination in all areas examined from animals kept in short photoperiods. In long photoperiods, 5-HT in the hypothalamus (particularly the anterior region) increased during the first 6 h after onset of light and levels in the pineal became arrhythmic. There were no differential effects of light on 5-HIAA/5-HT ratios. Removal of the pineal or the superior cervical ganglia abolished these differential rhythms, as did subcutaneous implants of oestradiol (releasing about 5 micrograms/day). Melatonin (1 mg/day) injected 8 h after the onset of light into animals kept in long photoperiods resulted in circadian 5-HT rhythms resembling those from animals exposed to short photoperiods, whereas melatonin given at 14 h after onset of light did not have this effect. It is suggested that 5-HT containing neural systems may play a role in the way the pineal transmits information about the duration of the photoperiod to the neural structures controlling the pituitary.

Animals↗