FMRFamide-like Peptides in the Nervous and Endocrine Systems of the Digenean Helminth Echinostoma liei

FMRFamide-like immunoreactivity has been demonstrated in the digenean trematode Echinostoma liei. The functions of FMRFamide-like substances appear to be many and varied within the invertebrates, where they are involved in neurotransmission, cardiovascular regulation, muscular contraction and/or relaxation, and in co-ordination of growth and maturation. It is clearly indicated that FMRFamide-like substances function as neurotransmitter/neuromodulator in E. liei by the abundance of positively stained nerve fibres and perikarya seen throughout the CNS and PNS. A single endocrine-like cell also showing FMRFamide-like immunoreactivity is situated within the muscular cirrus pouch.     

Glucose utilization by enzymatically-formed trophoblastic vesicles and Day-14 porcine blastocysts

The total glucose metabolism of 48-h spherical trophoblastic vesicles, Day-60 trophoblastic vesicles sections and Day-14 porcine blastocyst sections was measured by the method of O'Fallon and Wright (1). Trophoblastic vesicles were formed by enzyme dispersal in Day-14 porcine blastocysts. Glucose was based on DNA content of the tissue measured by diamino benzoic acid reaction with DNA (2). Slope of the lines (PMoles glucose utilized/4 h x DNA content) was different between Day-14 blastocyst sections and 48 h trophoblastic vesicles (P /= 0.05). Slopes of the lines were identical between 48-h trophoblastic vesicles and Day-60 trophoblastic vesicles sections (P >/= 0.87). Average glucose utilization on a per ng DNA basis was calculated. Day-14 blastocyst sections utilized 0.67 Pmoles glucose/4 h per ng DNA, Day-60 trophoblastic vesicles sections; 0.57; and 48-h sperical trophoblastic vesicles used 0.29. It is hypothesized that the change in glucose utilization between the Day-14 porcine blastocyst and enzymatically formed trophoblastic vesicles may be due to a decrease in metabolism as a consequence of in vitro culture. Further, it is theorized that Day-60 trophoblastic vesicles sections used higher quantities of glucose than 48-h sperical trophoblastic vesicles on a per ng DNA basis due to the increased availability of glucose to the cells of the inner layers, caused by the sectioning of the tissue. The results of this study identify changes in glucose metabolism of enzymatically formed porcine trophoblastic vesicles during culture. It is proposed that enzymatically-formed trophoblastic vesicles be used as a model system for the study of embyro metabolism.     

Dissociation of the effects of neuropeptide Y on feeding and memory: evidence for pre- and postsynaptic mediation

In mice not deprived of food, centrally administered neuropeptide Y (NPY) increases feeding and improves retention. In this study, we examined the effect of C-terminal NPY fragments on feeding and on memory retention. Mice were trained to avoid footshock in a T-maze. After training NPY, NPY fragments (20-36 and 26-36) or saline were administered intracerebroventricularly. Food consumption was measured during the first hour after training and memory retention was measured one week after training. NPY elicited a 544% increase in feeding compared to the saline control. Neither NPY fragment significantly increased feeding. Both NPY and NPY(20-36) improved retention compared to the saline-treated group. NPY(26-36) did not improve retention. NPY administered to well-trained mice results in amnesia. As a further test of the differential effect of NPY on memory processing and eating, we determined in well-trained mice whether administration of NPY and NPY(20-36) resulted in amnesia. Both NPY and NPY(20-36) resulted in amnesia, but only NPY stimulated feeding. These results are compatible with NPY effects on feeding being mediated through postsynaptic (Y1)NPY receptors and effects on memory retention being mediated through presynaptic (Y2)NPY receptors.     

Two-drug combinations of memory enhancers: effect of dose ratio upon potency and therapeutic window, in mice

Two-drug combinations have been reported to enhance retention more effectively than when either drug was administered alone at the same dose. Some combinations of cholinergic drugs enhance retention even though the total drug dosage is reduced by as much as 97% compared to the dose needed to improve retention when the same drugs are administered singly. The choice of dose ratio is usually arbitrary or based on empirical results. The present study systematically varied the ratio of two drugs in a combination and at the same time varied the dosage of each drug. The drug combinations were administered to mice immediately after training on T-maze footshock avoidance task. Retention was tested one week later. Three two-drug combinations were selected for presentation because they differed considerably as to (a) the lowest effective total dose that improved memory-retention, (b) the optimal ratio that improved retention and (c) the width of the therapeutic window. The effect of a drug combination on retention was found to be dependent on the particular drugs in the combination, the ratio and the dose administered.     

Genome instability in interspecific cell hybrids I. Unstable expression of genes in divergent cell hybrids

Somatic cell hybrids between cells of widely divergent mammalian species display a range of chromosomal and genetic anomalies which may be the equivalent of the “genomic shock” phenomena observed in many plant and animal interspecific hybrids. Mouse-kangaroo hybrids show extreme segregation and fragmentation of the kangaroo chromosomes. Here 1 show that, in addition to the chromosomal instability, some hybrids display unstable expression of three genes borne on the kangaroo active maternal X chromosome. These genes (HPRT, G6PD andPGK) may be co-ordinately inactivated at high frequency, then reactivated once more. I suggest that this reversible inactivation in interspecific hybrids may be the result of an unstable change at an X inactivation centre located in the kangaroo X_q.     

Immunoregulatory role of Ig isotypes. II. Activation of cells that block induction of contact sensitivity responses by antibodies of IgG2a and IgG2b isotypes

The influence that the isotype of Ag-specific antibody has on the induction of contact hypersensitivity (CS) has been investigated. Injection (i.v.) of mice with haptenated peritoneal exudate cells (PEC) pretreated with anti-hapten mAb of the IgG2a and IgG2b isotypes results in the activation of Ag-specific afferent acting Ts cells (Ts-aff). These suppressor cells are not generated when animals are injected with anti-hapten antibodies of other isotypes. The Ts-aff cells function to inhibit the generation of CS responses when injected into naive animals. Suppression is due to the induction of both Lyt-1+,2- I-J+ and Lyt-1-,2+ I-J+ T cells, both of which adhere to the lectin Vicia villosa. Attachment of both TNP and 4-ethoxymethylene-2-phenyloxazolone haptens to the same PEC, followed by treatment with an IgG2a anti-TNP antibody, generates Ts-aff cells specific for both 4-ethoxymethylene-2-phenyloxazolone and TNP. The MHC haplotype of the PEC is irrelevant, as allogeneic PEC will also induce Ts-aff cells when injected by using an identical protocol. Ts-aff cells cannot be generated in B cell-depleted mice, nor does the Ts-aff cells generated in normal mice suppress CS responses in B cell-depleted mice. These results show that Ag-antibody complexes bound on the surface of a PEC can induce potent afferent suppression in vivo. A possible general role for antibody isotypes in directing regulatory activities is discussed.     

The cytogenetic and hepatotoxic effects of dioxin on mouse liver cells

The cytogenetic and hepatotoxic effects of 2,3,7,8-tetrachlorodibenzo p-dioxin (TCDD) on mouse liver cells were investigated. Male C57BL/6J strain mice, which have TCDD receptors, were given single intraperitoneal injections of 25, 37.5, 75 and 150 g of TCDD/kg body weight or corn oil carrier alone. Two-thirds hepatectomies were carried out at 1 or 7 days after injection and chromosomal aberrations and mitotic indexes of the regenerating hepatocytes were scored 54 hr after hepatectomy. Liver sections from additional intact mice were studied for TCDD-hepatotoxicity at 1, 7 and 30 days after injection. The three high doses of TCDD caused hepatotoxicity with necrosis of liver cells and focal architectural collapse by 30 days after injection. No evidence was obtained of an increase in the frequency of chromosomal structural aberrations at doses that allowed sufficient mitotic activity for cytogenetic evaluation. We conclude that TCDD is not a clastogen for mouse hepatocytes, although high doses cause marked hepatocellular necrosis.Abbreviations CSD chromosome deletion - META metacentric chromosome - TCDD 2,3,7,8-tetrachlorobenzo-p-dioxin     

Differential effects of amylin on memory processing using peripheral and central routes of administration.

Amylin is a peptide hormone secreted from the beta cells of the pancreatic islets. Amylin was administered peripherally or centrally following weak or strong training on footshock avoidance conditioning in a T-maze. Under conditions of weak training, amylin improved memory retention in a dose-dependent manner. Under conditions of strong training, it impaired retention over the same dose range. Central administration of amylin in mice given strong training impaired retention but had no effect on the retention of mice given weak training. These findings suggest that the mechanisms of action by which amylin altered memory processing are different for peripheral and central administration. Peripherally secreted amylin may play a role in the amnesia seen in diabetes and the memory enhancement following glucose administration.