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PubMed1997

Galanin inhibits continuous and phasic firing in rat hypothalamic magnocellular neurosecretory cells.

The effects of galanin (GAL) on magnocellular neurosecretory cells (MNCs) were examined during microelectrode recordings from supraoptic neurons in superfused hypothalamic explants. Application of the full-length peptide (GAL1-29) or of the N-terminal fragment GAL1-16 produced reversible membrane hyperpolarization with an IC50 near 10 nM. These effects were associated with an increase of membrane conductance, with a reversal potential near -70 mV, and were not blocked by tetrodotoxin, indicating that the receptors mediating these effects are located postsynaptically. Hyperpolarizing responses were also observed in response to the GAL-like chimeric ligands M35 and M40, suggesting that these behave as partial agonists at galanin receptors. The reversal potential of the GAL-mediated effect was unaffected by reducing extracellular chloride or by intracellular chloride injection, indicating that the effects of galanin are not mediated by modulation of chloride conductances. In contrast, reducing the external concentration of potassium ions from 3 to 1 mM shifted the reversal potential of the responses to -85 mV, suggesting the involvement of a potassium conductance. When tested on spontaneously active MNCs, the hyperpolarizing effects of galanin were associated with a suppression of firing in both continuously active and phasically active neurons. Inhibition of phasic bursts was mediated both through the inhibitory effects of the hyperpolarization and through a GAL-mediated inhibition of the depolarizing afterpotential that is responsible for the production of individual bursts. These results suggest that galanin may be a potent endogenous modulator of firing pattern in hypothalamic neuroendocrine cells.

Action Potentials↗
PubMed1979

Delayed hypersensitivity to Staphylococcus aureus in mice: in vivo responses to isolated Staphylococcal antigens.

The development of delayed hypersensitivity (DH) to Staphylococcus aureus in Swiss mice was evaluated by the footpad (FP) assay. In order to determine which component of the bacteria was responsible for the in vivo immune reactivity, purified Staphylococcal cell wall, cell membrane, protein A, lipoteichoic acid, teichoic acid, as well as lipid-free membrane proteins were isolated. The immune responses of mice receiving one to eight S. aureus injections indicated that the first DH peak, following three injections, was primarily dependent upon protein antigens associated with the bacterial membrane. Increased bacterial injections gave rise to a second DH peak following seven injections which was dependent upon multiple bacterial components including cell wall, protein A, and membrane proteins.

Animals↗
PubMed1997

Specific histologic and cytogenetic evidence for in vivo malignant transformation of murine host cells by three human prostate cancer cell lines.

The chromosomal constitutions of three murine cell lines that developed in vitro from tumors that grew in nude mice after orthotopic and ectopic injections of three human prostate tumor cell lines were examined by histopathology, conventional G-banding, and with fluorescence in situ hybridization techniques. All three murine cell lines showed unique marker chromosomes involving mouse chromosome 12, with a common break point. Histopathologic evidence from a murine prostate gland into which SP 3031 cells had been injected indicated dysplastic glandular epithelium and carcinomatous areas. These observations further indicate that: (a) human prostate tumors are capable of transforming host organ cells, (b) host cells have specific chromosomal alterations that may be associated with transformation, and (c) the process of host cell transformation can be demonstrated in histological sections. Although cancer cell heterogeneity and drug-resistant phenotypes are caused by additional genetic alterations and clonal evolution of the original tumor, transformation of the host's distant organ cells may also contribute because most therapies are directed only to the original cancer cells.

Animals↗
PubMed1998

Primary neural precursors and intermitotic nuclear migration in the ventricular zone of adult canaries.

New neurons continue to be born in the ventricular zone (VZ) of the lateral ventricles in the brain of adult birds. On the basis of serial section reconstruction and electron microscopy, we determined that the VZ of the adult canary brain is composed of three main cell types (A, B, and E). Type A cells were never found in contact with the ventricle and had microtubule-rich processes typical of young migrating neurons. Type B cells were organized as a pseudostratified epithelium, all contacted the ventricle, and most had a characteristic single cilium. Type E cells, also in contact with ventricle, were ultrastructurally similar to the mammalian multiciliated ependymal cells. After six injections of [3H]-thymidine (1 every 12 hr), Types A and B cells were found labeled. Type E cells were never [3H]-thymidine labeled. One to two hours after a single injection of [3H]-thymidine, all labeled cells corresponded to Type B cells. At survivals of 5, 24, and 74 hr after [3H]-thymidine injection, the proportion of labeled Type B cells decreased and that of Type A cells increased, indicating that Type B cells were the primary precursors. Most [3H]-labeled nuclei at 1-2 hr after [3H]-thymidine injection were separated from the ventricular cavity, but most of the mitotic cells were adjacent to the ventricle. This observation and measurements of the distance between labeled nuclei and the ventricular surface at 1, 5, 7, and 11 hr after [3H]-thymidine injection indicate that Type B cell nuclei move toward the ventricle to divide. This work reveals the architecture of the VZ in an adult vertebrate brain, identifies the primary precursor of new neurons, and describes nuclear translocation of these precursors during the cell cycle.

Age Factors↗
PubMed1998

Uptake of a boronated epidermal growth factor-dextran conjugate in CHO xenografts with and without human EGF-receptor expression.

An epidermal growth factor (EGF)-dextran-boron conjugate for targeting against EGF receptor-rich tumours was investigated regarding uptake and distribution in vivo. EGF served as the tumour-seeking part and dextran was the carrier for the potentially toxic boron. Nude mice carrying subcutaneous tumours on the flanks were injected with conjugate either i.v. or intratumorally. The xenografts were from Chinese hamster ovary cells transfected with the gene for the human EGF-receptor (CHO-EGFR), and these cells expressed the EGFR. Non-transfected cells without EGF-receptors (CHO) were used as controls. No accumulations in tumours could be observed following the i.v. injections but there were, in both tumour types, high accumulations in the liver. Following intratumoral injections the accumulations were higher in the CHO-EGFR tumours than in the CHO tumours. The tumour over blood and liver ratios were also higher for the CHO-EGFR tumours than for the CHO tumours. Thyroid accumulations after the intratumoral injections indicate different degradation patterns of the conjugate in CHO-EGFR animals than in CHO animals. In conclusion, after intratumoral injections the conjugate showed receptor-dependent binding to EGFR-rich tumours, and the tumour-to-blood and tumour-to-liver ratios were promising.

Animals↗
PubMed1998

Biological activity and brain actions of recombinant rat interleukin-1alpha and interleukin-1beta.

IL-1alpha and IL-1beta have potent effects on the central nervous system resulting in fever, activation of the hypothalamic-pituitary-adrenal axis and behavioural depression. These effects have mainly been studied in rats, using recombinant human and mouse IL-1. Because IL-1alpha and IL-1beta show some species specificity in the potency of their biological activities, the objective of the present work was to directly compare the effects of recombinant rat IL-1alpha and IL-1beta in the rat system as a first step to dissect out the mechanisms that are involved in these effects. In vitro, recombinant rat IL-1alpha and IL-1beta bound with the same affinity as human IL-1 to the rat insulinoma Rin m5F cell line that mainly expresses type I IL-1 receptors. This binding activated IL-1 receptors, as shown by induction of the synthesis of TNF-alpha mRNA. In vivo, recombinant rat IL-1alpha and IL-1beta enhanced body temperature, increased plasma levels of corticosterone and ACTH, and depressed social behaviour. All these effects were obtained at doses 100-1,000 fold lower when IL-1 was injected centrally than when it was administered peripherally, indicating that they are centrally mediated. The relative potencies of recombinant rat IL-1alpha and IL-1beta were not the same depending on the endpoint and the route of injection, indicating that different mechanisms are likely to be involved in the various effects of IL-1 on the brain.

Animals↗
PubMed1996

[Effect of norepinephrinergic system on ipalbidine analgesia].

Ipalbidine (Ipa) is a photoactive alkaloid isolated from the seeds of ipomoea hardwickki Hemsl. The analgesic effects of Ipa were determined by rat tail flick method. A dose-dependent analgesic effect was found after s.c. or i.c.v. administration of Ipa, but no analgesia was observed after intrathecal injection, indicating that the analgesic effect of Ipa is central in origin, and it acts mainly on supraspinal substrate. The analgesic effect induced by Ipa (60 mg.kg-1, s.c.) was markedly reduced by reserpine (2 mg.kg-1, i.p.) given 24 h before Ipa, which was reversed by combined administration with i.c.v. norepinephrine (NE). In addition, Ipa-induced analgesia was significantly attenuated by electrolytic lesion of bilateral destruction of locus coeruleus, and combined administration with diethyldithiocarbamate (200 mg.kg-1, i.p.), phentolamine (10 mg.kg-1, i.p. or i.c.v.), and prazosin (3 mg.kg-1, s.c.). But no influence was observed on the analgesia of Ipa after administration of yohimbine (5 mg.kg-1, s.c.) or propranolol (10 mg.kg-1, i.p.). These results suggest that the analgesia caused by Ipa is closely related to the function of the central norepinephrinergic system, and probably mediated by indirectly acting on alpha 1 receptors, but not alpha 2 or beta receptors.

Analgesics, Non-Narcotic↗