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J Herbert

Publications and source records attributed to J Herbert.

At least 145 records · Page 8Linked to original sources
PubMed1990

Distribution of transthyretin in the rat eye.

We reported previously synthesis of transthyretin (TTR), or prealbumin, a transport protein for thyroxine and retinol, in the eyes of rats and cows and showed that in the rat eye, TTR mRNA is localized exclusively in the retinal pigment epithelium (RPE). We now demonstrate by immunohistochemistry that TTR has a more widespread distribution in the rat eye than does its mRNA. Intense immunoreactivity for TTR was found in the RPE, ciliary epithelium, iris epithelium, corneal endothelium, optic nerve fiber layer of the retina, and lens capsule. Depending on the method of processing, immunoreactivity of varying intensity was found also in other ocular structures. In particular, the retinal ganglion cells were strongly immunoreactive on frozen sections but not on paraffin sections. Although vitreous humor was not included in the sections of adult rat eye, sections of a 25-mm rat embryo showed intense immunoreactivity in the vitreous humor. Since plasma TTR does not cross Bruch's membrane into the retina, our findings suggest that ocular TTR is synthesized, at least in part, in the RPE and is transported to specific locations within the eye. Although the physiologic role of ocular TTR is unknown, it is possible that it participates in retinol cycling within the eye. The widespread ocular distribution of TTR may account for the occurrence of various forms of ocular amyloidosis in the familial amyloidotic polyneuropathies, a group of dominantly inherited disorders caused by point mutations in the TTR gene.

Animals↗
PubMed1990

Comparative effects of preoptic area infusions of opioid peptides, lesions and castration on sexual behaviour in male rats: studies of instrumental behaviour, conditioned place preference and partner preference.

The effects on the sexual behaviour of male rats of excitotoxic amino acid-induced lesions of the medial preoptic area-anterior hypothalamic area (mPOA/AHA), infusions of beta-endorphin, alpha-melanocyte stimulating hormone and naloxone into the mPOA/AHA, systemic naloxone and castration were compared using different behavioural paradigms. These included measures of unconditioned copulatory behaviour, instrumental responses for an oestrous female presented under a second-order schedule of reinforcement, conditioned place preference and partner preference. The results demonstrate that manipulations of the mPOA/AHA markedly affect consummatory aspects of sexual behaviour (mounting, intromitting and ejaculating) but tend not to affect appetitive or reward-related aspects of sexual behaviour, although intra-mPOA/AHA alpha MSH did result in a small increase in instrumental responses, while beta-endorphin infused into the mPOA/AHA also abolished preference for an oestrous over an anoestrous female. Systemic naloxone, on the other hand, reduced instrumental behaviour and a place preference conditioned by prior sexual interaction, while the same compound infused into the mPOA/AHA markedly facilitated copulatory responses but did not affect other measures of appetitive sexual responses. Castration caused an extremely rapid attenuation of conditioned place preference which was apparent before the males had experienced reductions in their copulatory performance. This treatment only slowly reduced partner preference. The results indicate that the use of several behavioural procedures can reveal discrete actions of neuroendocrine treatments on separable psychological processes which underly the integrated pattern of masculine sexual behaviour. In particular, they suggest that the mPOA/AHA is especially concerned with the copulatory responses of mounting and intromitting, but is much less important for a variety of appetitive sexual acts as well as sexual reward, as measured in the place preference procedure. The marked effects of castration on conditioned place preference taken together with the lack of effect of lesions of the mPOA/AHA on this measure indicate that testosterone affects sexual reward-related processes by an action at a site other than the mPOA/AHA. The implications of these findings are discussed.

Animals↗
PubMed1990

Gonadal responses of the male Syrian hamster to programmed infusions of melatonin are sensitive to signal duration and frequency but not to signal phase nor to lesions of the suprachiasmatic nuclei.

This study investigated the roles of the melatonin signal and the circadian system in the induction of photoperiodic responses in the male Syrian hamster. Pinealectomized animals received programmed s.c. infusions of saline or melatonin. Saline infusions for 10 h or melatonin for 4 h during the night had no effect on the reproductive axis whereas nightly 10-h infusions of melatonin induced gonadal atrophy. Animals that received 10-h infusions of melatonin arranged such that consecutive daily signals were delivered alternately during the day and night also exhibited gonadal atrophy, whereas melatonin signals delivered every 48 h, exclusively during either the day or night, were without effect. These results demonstrate that the brain is able to read melatonin signals delivered at different phases of the circadian cycle and to use them in combination to generate an appropriate photoperiodic response. Melatonin signals lasting 10 h delivered to pinealectomized (PX) animals every 24 h induced gonadal regression. Melatonin delivered at periodicities of 20 h, 23 h, and 25 h also caused gonadal regression whereas infusions every 28 h were without effect, demonstrating that the systems responsive to melatonin are sensitive to signal frequency but do not need to receive the signal on a strictly circadian basis. These results are discussed in the context of the significance of the melatonin-free interval. PX animals that received sham or bilateral lesions of the suprachiasmatic nuclei (SCN) were infused nightly for 10 h with saline or melatonin. Melatonin infusions were equally effective at inducing gonadal atrophy and lowering serum testosterone levels in both sham- and SCN-lesioned animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

[Clinical variations of the so-called wedge-shaped defect].

Clinical variations of 288 so-called wedge-shaped defects were described at the model and in the clinic in 50 patients aged 21 to 67 years and classified according to depth, profile and en face contour. Defect formation starts in early adult age increasing in dependence on age. The term "wedge-shaped defect" is only partly indicative and incorrect.

Adult↗
PubMed1990

A marker for primary choroid plexus neoplasms.

Primary choroid plexus (CP) tumors are rare neoplasms that present in childhood or, less frequently, in adult life. The majority are benign and amenable to complete surgical excision, but occasionally more invasive variants are encountered. Although generally pathologically distinct, occasionally primary CP neoplasms may be difficult to distinguish from metastatic papillary carcinomas or papillary ependymomas. Conventional cytologic markers are not sufficiently specific to permit accurate diagnosis of primary CP tumors. The authors have reported that the CP is the unique site of synthesis within the brain of transthyretin (TTR, prealbumin), a transport protein for thyroxine and retinol. They therefore investigated the utility of TTR as a biochemical marker for CP tumors. They detected intense immunoreactivity for TTR at high dilutions of primary antiserum in the neoplastic epithelium of all of nine primary CP tumors (six papillomas and three carcinomas), but not in eight cellular or three papillary intracerebral ependymomas, meningiomas, oligodendrogliomas, astrocytomas, primary extracerebral papillary carcinomas (three thyroid, two breast) or five of six cerebral metastases from systemic papillary carcinomas. In one case of cerebral metastasis from papillary thyroid carcinoma, rare isolated immunoreactive cells were observed. Faint staining of the stromal-ependymal junction was seen in myxopapillary ependymomas of the filum terminale, which were otherwise nonreactive. By in situ hybridization, TTR mRNA was abundant in neoplastic CP epithelium, confirming local TTR synthesis. The authors conclude that TTR is synthesized by neoplastic CP epithelium and is an excellent marker for primary CP neoplasms.

Adolescent↗
PubMed1989

Neural systems underlying photoperiodic time measurement: a blueprint.

This paper briefly reviews the formal properties of the photoperiodic time measurement apparatus of mammals and presents a hypothetical model for the operation of the neural systems responsible for reading and responding to the nocturnal pineal melatonin signal. The primary melatonin readout mechanism is held to be common to all species responsive to melatonin. It seems likely that this mechanism responds to relative changes in the duration and amplitude of the melatonin signal, rather than the absolute levels of melatonin encountered. A series of neural systems which exploit the calendar information provided by the primary readout is envisaged to vary between and within species, depending upon the neuroendocrine response under consideration. Of particular importance is a mechanism for comparing the relative duration of successive melatonin signals. These more complex elements are responsible for phenomena such as the effects of photoperiodic history and photorefractoriness. The brain may be able to encode an accumulated memory of melatonin signals and thereby define longer term intervals within the annual cycle. A series of response elements within the hypothalamus are engaged by the appropriately processed photoperiodic stimuli. For all elements of this model, their anatomical representations are poorly understood or, in certain cases, completely unknown.

Animals↗
PubMed1989

A farewell to queues.

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Appointments and Schedules↗
PubMed1989

Biochemical properties of monoamine-rich human neuroblastoma cells.

The biochemical, pharmacological and immunological characterization of cells derived from human neuroblastoma tumors recently acquired great interest, since these cells may be a putative donor source for transplantation in animal models of neurological disorders. We measured monoamine levels, tyrosine hydroxylase (TH) immunostaining, and the expression of major histocompatibility cell surface antigens (MHC) in 7 human neuroblastoma cell lines. Three cell lines (LAN5, NB69 and CHP126) had high levels of monoamines. TH immunostaining was strongly positive in CHP126 and LAN5, and NB69. MHC were not detected in any of the cells with high catecholamine levels. Treatment with neuroleptics increased the metabolism of dopamine in LAN5 but not in NB69. The implantation of LAN5 cells in immunocompetent, unilaterally 6-hydroxydopamine-lesioned rats decreased the apomorphine-induced contralateral rotation. The effect of the implant was greatest in animals in which LAN5 neuroblastoma cells, pretreated with dibutyryl cyclic adenosine monophosphate (DBcAMP) and prostaglandin E1 (PGE1, were implanted into the cerebral ventricle ipsilateral to the lesion, and then irrigated with DBcAMP administered through a totally implanted drug delivery system. The effect of the implant decreased after the second week. Neuroblastoma cells were found in approximately 50% of the implanted animals. TH immunostaining was weak or absent in the grafted animals. Inflammatory changes were present in the majority of the brains examined. Extensive tumor growth was present in one animal implanted with untreated cells. Grafting of cells treated with DBcAMP and PGE1 plus with mitomycin C and bromodeoxyuridine in animals immunosuppressed with cyclosporin A reduced the apomorphine-induced rotation to 40-60% of baseline levels and this reduction persisted beyond the period of infusion with DBcAMP. Intraventricular infusion of DBcAMP in animals injected with cell culture medium produced a transient reduction of rotation to 70% of baseline. The amphetamine-induced rotation was not significantly reduced during the 4 weeks follow up. Atypical cells, consistent with surviving neuroblastoma cells, were observed in the brain of all transplanted animals. TH immunostaining was weak or negative in most cases. Human neuroblastoma cells may be an alternative donor tissue for the study of the effects of transplantation in animal models of Parkinson's disease.

Animals↗
PubMed1989

Differential effects of beta-endorphin infused into the hypothalamic preoptic area at various phases of the male rat's sexual behaviour.

Beta-Endorphin, infused into the pre-optic/anterior hypothalamus (40 pmoles bilaterally) of the male rat before he was placed in an arena containing an oestrous female, inhibited mounting, intromitting and ejaculation, but investigative behaviour continued at control levels. If the infusion was delayed until the male had made an intromission, then beta-endorphin no longer had any effect on sexual interaction, the male mounting and ejaculating as if he had received a control infusion of artificial cerebrospinal fluid. However, if the male was returned to a different female after the infusion had been completed, then the suppressive effects of beta-endorphin returned. Males infused during the refractory period following an ejaculation (and returned to the same female) showed unimpaired return of sexual activity. Imposing a delay of up to 2 h after an intromission and an infusion showed that the effect of beta-endorphin was still antagonized when the male was again paired with the same female; however, by 6 h, its inhibitory effects were beginning to return. Allowing the male to mount (but not intromit) a female whose vagina had been taped partially counteracted the behavioural effect of beta-endorphin. If the female was separated from the male by a small wire cage which allowed limited interaction with her, subsequently infusing the males with beta-endorphin suppressed their mounting behaviour. These results show that both investigative and mounting behaviour can occur after infusions of beta-endorphin into the pre-optic/anterior hypothalamus, but that the transition between them is prevented if infusions are made before a critical point in the behavioural sequence. This is the onset of following the female and mounting her. Analysis of the behavioural sequence after either artificial cerebrospinal fluid or beta-endorphin infusions confirmed this; beta-endorphin interrupted the sequence at the first transition between investigative and mounting behaviour. These results suggest that beta-endorphin acts on a neural mechanism in the medial preoptic area/anterior hypothalamus which allows matching of incentive stimulus to specific behavioural response, and this may be a general property of this part of the brain.

Animals↗
PubMed1989

Photoperiodic influences on sexual behavior in male Syrian hamsters.

The effect of photoperiodic conditions on sexual behavior was investigated in male Syrian hamsters that were either gonadally intact, or castrated and treated with low doses of testosterone throughout the experiment. Hamsters were exposed to long (LD 16:8) or short (LD 8:16) days for 7 weeks; for the next 8 weeks, either they were exposed to an intermediate daylength (LD 12:12), or daylength conditions remained unchanged. Sexual behavior was affected by photoperiod conditions in both gonadally intact animals and testosterone-treated castrates, but to different degrees. Intact males exposed to short days for 15 weeks exhibited gonadal regression, and their copulatory performance was impaired. The percentage of animals that intromitted or ejaculated was significantly reduced. Additional measures of sexual performance among the copulating males were also affected. In contrast, among the castrates with testosterone clamped at low but stable levels, the proportion of males that mounted, intromitted, or ejaculated was not affected by photoperiod. However, among the males that continued to copulate, sexual performance changes were present in the short-day castrates that resembled those displayed by the intact males. We infer that these behavioral effects in both hormonal conditions reflect primarily a difficulty in the attainment of intromission. Gonadal regression alone cannot easily account for the behavioral deficits of the intact males, because circulating testosterone levels at the end of the experiment were not significantly different between the gonadally intact hamsters and the castrated, testosterone-treated hamsters exposed continuously to short days. Males transferred from either long or short days to the intermediate-daylength condition responded behaviorally to this photoperiod as if it were a short day, that is, their ejaculatory frequency declined. We conclude that male hamsters exposed to photoinhibitory daylengths exhibit deficits in their sexual behavior, not only because endogenous levels of testosterone decrease, but also because the substrates on which this hormone acts become less responsive. We hypothesize that under physiological conditions, the episodic secretion of testosterone imposes constraints on the maintenance or restoration of copulation, and that the potent behavioral effects achieved by constant-release implants of testosterone may mask the presence of photoperiodically induced alterations in the hamster's sensitivity to this gonadal hormone.

Animals↗
PubMed1989

Differential effects of photoperiodic history on the responses of gonadotrophins and prolactin to intermediate daylengths in the male Syrian hamster.

The effect of photoperiodic history on the neuroendocrine response to intermediate daylengths (11-13.5 hr of light) was investigated in the male Syrian hamster. The duration of the nocturnal peak of pineal melatonin content was inversely proportional to photoperiod and independent of photoperiodic history. Serum levels of prolactin were lower in animals exposed to shorter photoperiods. Photoperiodic history had little effect on the response of serum prolactin to intermediate daylengths. Serum luteinizing hormone (LH) concentrations were also lower in shorter photoperiods, but in addition were sensitive to the direction of photoperiodic change, so that a single photoperiod could be interpreted as either stimulatory or inhibitory to LH secretion. This effect of photoperiodic history was expressed at intermediate photoperiods with 12-13.5 hr of light. The sensitivity of serum follicle-stimulating hormone (FSH) levels to photoperiodic history was masked by an early onset of photorefractoriness. Testicular size and serum testosterone levels revealed weaker effects of photoperiodic history; these were attributed to the dissociation between gonadotrophin and prolactin secretion induced by intermediate daylengths. The contrasting effects of photoperiodic history on the secretion of LH and prolactin may represent the expression of multiple photoperiodic time-measuring systems.

Aging↗
PubMed1989

The hypothalamus and photoperiodic control of FSH secretion by melatonin in the male Syrian hamster.

In the photoinhibited castrated male Syrian hamster, removal of the pineal gland or transfer to long photoperiods was followed by a rapid increase in the serum concentration of FSH. Levels were significantly above those of controls within 10 days. Central passive immunization of pineal-intact photoinhibited castrated animals against melatonin had a stimulatory effect on serum FSH levels, comparable with that observed following pinealectomy or transfer to short days. The effects of pinealectomy were blocked by programmed s.c. infusions of melatonin in a time-dependent manner. Serum FSH levels remained low in animals receiving 100 ng melatonin delivered over 10 h but the same mass of melatonin delivered over 4 h had no effect on the response to pinealectomy. Lesions of the anterior hypothalamus had no effect on the pinealectomy-induced increase of serum FSH in animals receiving saline infusions. However, in lesioned animals, programmed infusions of melatonin were no longer able to suppress the rise in FSH following pinealectomy. These results demonstrated that pineal melatonin is the mediator of central photoperiodic control of FSH secretion. The duration of the melatonin signal determines its effectiveness and an intact anterior hypothalamus is necessary for the signal to be read and/or the appropriate neuroendocrine response expressed.

Animals↗
PubMed1989

Widespread expression of amyloid beta-protein precursor gene in rat brain.

The neuritic plaque is a characteristic finding in Alzheimer's disease. A major component of the plaque core is a 4.2 kd polypeptide, amyloid beta-protein (ABP), which is derived from the C-terminus of a larger precursor protein (ABPP). The authors have studied the transcription of ABPP mRNA in the adult rat brain by Northern analysis and in situ hybridization, and report that the ABPP gene gives rise to essentially the same multitranscript family of mRNAs as in the human, and that differential transcription patterns exist between brain and kidney. Morphologically, ABPP mRNA is expressed ubiquitously in neurons of the fore and hindbrain. ABPP transcripts also are present less frequently in occasional glial cells and at moderate to low frequency in nonneural cell types, namely, the choroid plexus epithelium, ependymal cells, and leptomeningeal membranes. Neuronal transcripts are most abundant in cerebral cortical layers II and V, the pyramidal cell layer of the hippocampus, the olfactory cortex, nucleus basis pontis, cranial nerve nuclei, and, significantly, in Purkinje cells and cerebellar granule cells. Because the cerebellum is relatively uninvolved in Alzheimer's disease, these findings suggest that high intraneuronal expression of ABPP may be a necessary but not sufficient requirement for plaque formation.

Alzheimer Disease↗
PubMed1988

Retinol-binding protein is synthesized in the mammalian eye.

As the chromophoric component of the visual pigment, retinol plays an essential role in vision. In the plasma, retinol is transported by retinol-binding protein (RBP) in complex with transthyretin (TTR, prealbumin). In previous work we demonstrated intraocular synthesis of TTR. To determine whether RBP is also synthesized in the eye, we performed Northern and Western blot analysis of rat eye, and detected both RBP mRNA and immunoreactive RBP. Regional Northern analysis of bovine eye localized RBP mRNA to ciliary body/iris and retina/RPE. Preliminary immunohistochemical studies revealed a widespread but heterogeneous distribution of RBP in rat eye. We postulate that ocular RBP and TTR are involved in the intraocular translocation of retinol.

Animals↗
PubMed1988

Non-chromaffin tissue plus nerve growth factor reduces experimental parkinsonism in aged rats.

The mechanisms by which intrastriatal grafts of chromaffin tissue alleviate the signs of clinical and experimental parkinsonism remain elusive. In the present report, we have demonstrated that, in conjunction with intraventricular infusion of nerve growth factor (NGF), ventricular grafts of either non-chromaffin or adrenal medullary tissue are equally effective in reducing apomorphine-induced circling in rats whose substantia nigra have been permanently lesioned with 6-hydroxydopamine. These treatments were much more effective than implantation of adrenal medulla without NGF. In addition, the effects persisted indefinitely, though at a reduced level, after discontinuation of the NGF infusion. The results suggest that trophic factors may be crucial to the beneficial effects of intracerebral transplanted tissues.

Adrenal Medulla↗
PubMed1988

Transthyretin is synthesized in the mammalian eye.

Transthyretin (TTR, prealbumin) is a 55 kDa protein which plays an important role in the plasma transport of thyroxine and retinol. Although the liver and choroid plexus are the two major known sites of TTR synthesis, several lines of evidence suggest the possibility of a separate ocular source of TTR. We report the presence of TTR mRNA in rat and bovine eye and of TTR in rat eye. Preliminary immunohistochemical data indicate that the retinal pigment epithelium is a major site of TTR immunoreactivity in the rat. While the functional significance of ocular TTR synthesis is unclear, TTR may be involved in the ocular translocation and processing of retinol. The finding of TTR synthesis in the eye may explain ocular involvement in the familial amyloidotic polyneuropathies.

Animals↗