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Biomedical subjects

R H Porter

Publications and source records attributed to R H Porter.

At least 55 records · Page 3Linked to original sources
PubMed1993

NMDA and AMPA receptors in transgenic mice expressing human beta-amyloid protein.

The human beta-amyloid protein may play an important, possibly primary, role in the pathogenesis of Alzheimer's disease (AD), and it appears to potentiate the susceptibility of neurons to excitotoxicity. AD is associated with alterations in the N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) subtypes of glutamate receptors, and it has been suggested that excitotoxicity may play a role in neuronal damage in AD. In this study, we have used quantitative receptor autoradiography to examine NMDA and AMPA receptors in transgenic mice that contain the gene for the carboxyl-terminal 100 amino acids of the human amyloid precursor protein, beginning with the beta-amyloid region, which is under the control of the JC viral early region promoter. Reverse transcriptase-polymerase chain reaction confirmed that the brains of transgenic mice expressed beta-amyloid mRNA and that control mice did not. NMDA receptors, assessed with [3H]MK-801, were unchanged in the transgenic compared with the control mice. In the transgenic mice, there were no significant changes in [3H]AMPA receptor binding compared with controls. This study represents the first attempt to evaluate in transgenic mice the in vivo interaction between beta-amyloid expression and excitatory amino acid receptors.

Amyloid beta-Peptides↗
PubMed1992

L-aspartate-beta-hydroxamate exhibits mixed agonist/antagonist activity at the glutamate metabotropic receptor in rat neonatal cerebrocortial slices.

L-aspartate-beta-hydroxamate, a glutamate uptake inhibitor, was investigated for activity at a glutamate metabotropic receptor (mGluR) in neonatal rat cerebral cortical slices. Stimulation of phosphatidylinositol hydrolysis by 100 microM (1S,3R)-ACPD was inhibited only very weakly, to a maximal extent of 28%, L-aspartate-beta-hydroxamate did however exhibit agonist activity (EC50 = 760 microM) and, although much less potent than (1S,3R)-ACPD (EC50 = 20 microM), its efficacy was approximately 70% of the latter. These results indicate that, at least in this preparation, offspartate-beta-hydroxamate is of little value as an antagonist at the mGluR receptor.

Animals↗
PubMed1992

Modulation of [3H]3-((+-)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid ([3H]CPP) binding by ligands acting at the glycine and the polyamine sites of the rat brain NMDA receptor complex.

The competitive N-methyl-D-aspartate (NMDA) receptor antagonist [3H]3-((+-)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid ([3H]CPP) interacts with two discrete binding sites, one of high- and the other of low-affinity, on rat forebrain synaptic plasma membranes. The high affinity site exhibited a Kd of 101.5 nM and a Bmax of 2.01 pmol/mg, while for the low affinity site the Kd was 4.11 microM with a Bmax of 19.7 pmol/mg. The glycine site antagonists 3-amino-1-hydroxy-2-pyrrolidone (HA-966), 1-aminocyclobutanecarboxylic acid (ACBC), the glycine site agonist 1-aminocyclopropanecarboxylic acid (ACC) and glycine itself (as well as the polyamines spermine and spermidine), enhanced [3H]CPP binding. When subjected to saturation analysis, this enhancement was found primarily to involve an increase in the affinity of the high affinity component of [3H]CPP binding. Neither of the parameters of the low affinity component of binding were affected. Although a similar enhancement was observed with the polyamines, the effects of these two classes of ligands were additive, consistent with their having actions at different recognition sites on the NMDA receptor complex.

Amino Acids↗
PubMed1992

Heterogeneity of NMDA receptors labelled with [3H]3-((+-)-2-carboxypiperazin-4-yl) propyl-1-phosphonic acid ([3H]CPP): receptor status in Alzheimer's disease brains.

The binding of [3H]3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid ([3H]CPP) was studied in rat and human brain synaptic membranes. Specific binding was saturable, reversible and inhibited by a range of compounds active at N-methyl-D-aspartate (NMDA) receptors such as 2-amino-5-phosphonopentanoate (AP5), 2-amino-7-phosphonoheptanoate (AP7), NMDA and cis-2,4-methanoglutamate. Binding was heterogeneous as evidenced by non-linear Scatchard plots and Hill coefficients for binding inhibitors significantly different from unity. LIGAND analysis of the binding data indicated the likely presence of two distinct binding components for CPP, one of high (Kd values approx. = 70 nM) and the other of low (Kd values approx. 5 microM) affinity. Possible alterations in the binding of [3H]CPP to either site were investigated in medial frontal and medial temporal cortex from Alzheimer's disease brains and compared with control tissues, carefully matched for age and postmortem delay. While there were considerable inter-individual variations in binding, no significant differences were detected either between brain regions in either Alzheimer or control subjects, or between Alzheimer's disease and control brains. These data suggest the presence of at least two components of [3H]CPP binding in both rat and human brain tissue. The integrity of neither of these components is altered in Alzheimer's disease, consistent with a lack of gross alterations of NMDA receptors in this disorder.

2-Amino-5-phosphonovalerate↗
PubMed1992

(S)-homoquisqualate: a potent agonist at the glutamate metabotropic receptor.

The synthetic quisqualate analogue, (S)-homoquisqualate was examined for activity at the glutamate metabotropic receptor, in relation to its ability to stimulate phosphoinositide hydrolysis in rat pup cerebro-cortical slices. The compound produced a robust increase in hydrolysis (EC50 = 50.2 +/- 1.6 microM), which, in common with responses to quisqualate and (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate ((1S,3R)-ACPD), was antagonized uncompetitively by L-2-amino-3-phosphonopropionate (L-AP3). In contrast to quisqualate which exhibits low efficacy, (S)-homoquisqualate behaves as a full agonist at the metabotropic receptor.

Animals↗
PubMed1991

Individual olfactory signatures as major determinants of early maternal discrimination in sheep.

Responses of recently parturient ewes to their familiar versus separated (i.e., unfamiliar) twin lambs were observed in an attempt to elucidate further the characteristics of the phenotypic traits (signatures) mediating maternal recognition and bonding. Ewes responded more positively to their familiar lamb than to its twin that had been isolated at birth. Nonetheless, those same mothers also discriminated between their separated twin and unfamiliar alien lambs. Alien lambs elicited similar rejection behavior regardless of whether they had been housed with their own mother or in isolation prior to testing. Lambs appear to have individually distinct (olfactory) signatures; however, the signatures of twin siblings may be sufficiently similar to enable the mother to detect a resemblance. No evidence suggests that acquired maternal labels play a role in either the acceptance of the ewe's own lamb(s) or rejection of aliens.

Animals↗
PubMed1991

An assessment of the salient olfactory environment of formula-fed infants.

Olfactory preferences of two-week-old bottle-fed infants were assessed in a series of simultaneous two-choice tests. Infants of each sex displayed preferential orientation to a stimulus pad worn on their mother's breast over a clean control pad. When maternal breast odor was paired with the odor of the infants' formula, however, boys spent more time oriented toward the formula odor, whereas girls evinced no reliable preferences. Although the subject infants had no prior direct contact with odors emanating from the breasts of lactating females, but had recurring reinforced exposure to the odor of their familiar formula (in the context of feeding), the former scents elicited a more positive response. Preferential orientation to lactating-breast odors reflects adaptive inborn attraction to cues associated with the natural food source for human neonates.

Attention↗
PubMed1990

The influence of maternal labels on dietary preferences of spiny mouse weanlings.

To assess the influence of conspecific chemical cues on the development of dietary preferences, spiny mouse (Acomys cahirinus) weanling were tested for their responses to food items that were partially eaten (thus, presumably labeled) by various categories of conspecifics. Consumption of a highly preferred novel food (fresh carrot) labeled by the pups' parents, or mother alone, was greater than that of a clean sample of the same food. The presence of labels emanating from the father or an alien mother had no effect on food consumption. Salient maternal labels that elicit preferential feeding by young appear to be individually unique, therefore allowing pups to recognize such cues emanating from their own mother. The attractive substance that mothers transfer to food items while eating (the maternal label per se) has not been identified, but saliva is a likely candidate.

Animals↗
PubMed1989

Mechanisms and ecological correlates of kin recognition.

Kin recognition, which can be inferred from differential interactions amongst close relatives as compared to unrelated conspecifics, has been documented in a wide range of vertebrates and invertebrates. Kin may be discriminated by phenotypic traits (signatures) that are genetically mediated, acquired from the environment, or arise from an interaction between these two sources. The developmental mechanisms underlying recognition of relatives (or their signatures) include direct contact and familiarization, indirect familiarity (whereby previously unencountered individuals are recognized by their resemblance to familiar kin) and hypothetical recognition alleles. The biological significance and mediating mechanisms of kin recognition vary across species according to their ecology and natural history. To illustrate this point, the results of laboratory and field studies of larvae of several species of toads and frogs are reviewed.

Animal Communication↗
PubMed1989

Attractiveness of lactating females' breast odors to neonates.

A series of experiments investigated the responses of human infants to olfactory cues produced by lactating females. 2-week-old bottle-feeding girls oriented preferentially to the breast odor (odorized pad) of a nursing woman when paired with such odors from either a nonparturient female or axillary odors from the same lactating female. Responses to axillary odor from a lactating female did not differ from those to a clean (nonodorized) pad. These data indicate that breast odors from lactating females are especially attractive to female infants who are unfamiliar with the stimulus woman and who have had no prior breast-feeding experience.

Axilla↗
PubMed1987

Effects of intranasal ZnSO4 irrigation are mitigated by the presence of untreated littermates.

Observable anomalies were produced in spiny mouse neonates and weanlings through intranasal irrigation with ZnSO4 solution. In comparison to control animals, ZnSO4-treated pups displayed growth retardation, increased mortality rates, hyperactivity in a novel environment and difficulty in finding hidden food pellets. Each of these experimentally-induced deficits was alleviated when treated pups were housed and tested in the presence of intact littermates. The early social environment exerts marked influences on behavioral and physiological development and, if optimal, can buffer pups from the adverse effects of early physical insults.

Administration, Intranasal↗
PubMed1986

Physical and behavioral sequelae of low birthweight in spiny mice (Acomys cahirinus).

Physical and behavioral sequelae of low birthweight (LBW) were investigated in spiny mice (Acomys cahirinus). When raised by their biological mother, pups whose Day-2 weights were 1 SD or more below the population mean remained smaller through the first 30 days postpartum than pups born within normal (N) weight ranges. LBW pups fostered onto mothers who gave birth to N pups gained weight more rapidly than LBW pups remaining with their own mother. Similarly, N pups fostered onto mothers of LBW pups displayed reduced weight gain relative to N siblings raised by their biological mother. It appears that rate of weight gain is influenced by an interaction between birthweight and maternal rearing environment. LBW pups also were less responsive than N pups to maternal chemical cues, indicating that low birthweight is correlated with deficits in adaptive behavior.

Animals↗
PubMed1985

Odor signatures and kin recognition.

The basis of olfactory signatures mediating human kin recognition was investigated in two experiments. The odors of mothers and offspring were correctly matched (by subjects unfamiliar with the stimulus individuals) at a greater than chance frequency. In contrast, subjects were not able reliably to match the odors of husbands and wives. These data support the hypotheses that characteristic individuals odors are genetically mediated and that kin recognition should be facilitated by the similarity of such familiar odors among close relatives.

Adolescent↗
PubMed1985

Recognition of maternal axillary odors by infants.

A series of 5 experiments was conducted to determine whether neonates, at approximately 2 weeks of age, can recognize their parents through axillary odors alone. Breast-feeding infants discriminated between their mother's axillary odor and odors produced by either nonparturient or unfamiliar lactating females. In contrast, breast-feeding infants displayed no evidence of recognizing the axillary odors of their father. Likewise, bottle-feeding infants appeared unable to recognize the odor of their mother when presented along with odors from a nonparturient female or an unfamiliar bottle-feeding female. Several hypotheses were presented in an attempt to account for the differential reactions to maternal odors by breast-feeding versus bottle-feeding infants. It was tentatively concluded that, while breast-feeding, infants are exposed to salient maternal odors and thereby rapidly become familiarized with their mother's unique olfactory signature.

Axilla↗