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Biomedical subjects

C A Nelson

Publications and source records attributed to C A Nelson.

At least 91 records · Page 5Linked to original sources

Past, current, and future trends in infant face perception research.

Our review of infant face perception research had three purposes. First, we briefly attempted to describe a number of themes prevalent in the literature before 1979. Although the themes were broad and difficult to identify clearly, the underlying issues of the time seemed to fit three headings: (a) research that either did or did not support the existence of an innate preference for faces, (b) research that explored infants' general knowledge of faces, particularly their sensitivity to the invariant properties of faces, and (c) how infants acquire information about faces, as demonstrated through studies of facial scanning and feature discrimination. Our second goal was to summarize current trends. Here emphasis was placed on studies concerned with the face as a conveyer of socially-salient information, the neurological basis of face perception, and recent methodological innovations. Our final goal was to provide a sampling of issues and questions that seemed appropriate for investigation during the next decade.

Attention↗

Positive and negative selection of an antigen receptor on T cells in transgenic mice.

The T-cell repertoire found in the periphery is thought to be shaped by two developmental events in the thymus that involve the antigen receptors of T lymphocytes. First, interactions between T cells and major histocompatibility complex (MHC) molecules select a T-cell repertoire skewed towards recognition of antigens in the context of self-MHC molecules. In addition, T cells that react strongly to self-MHC molecules are eliminated by a process called self-tolerance. We have recently described transgenic mice expressing the alpha beta T-cell receptor from the cytotoxic T lymphocyte 2C (ref. 11). The clone 2C was derived from a BALB.B (H-2b) anti-BALB/c (H-2d) mixed lymphocyte culture and is specific for the Ld class I MHC antigen. In transgenic H-2b mice, a large fraction of T cells in the periphery expressed the 2C T-cell receptor. These T cells were predominantly CD4-CD8+ and were able to specifically lyse target cells bearing Ld. We now report that in the periphery of transgenic mice expressing Ld, functional T cells bearing the 2C T-cell receptor were deleted. This elimination of autoreactive T cells appears to take place at or before the CD4+CD8+ stage in thymocyte development. In addition, we report that in H-2s mice, a non-autoreactive target haplotype, large numbers of CD8+ T cells bearing the 2C T-cell receptor were not found, providing strong evidence for the positive selection of the 2C T-cell receptor specificity by H-2b molecules.

Animals↗

Selective expression of an antigen receptor on CD8-bearing T lymphocytes in transgenic mice.

The major problem in the study of T-cell development is that of tracking thymocytes of a given specificity. Recent studies have exploited natural correlations between the expression of a particular V beta gene segment and T-cell receptor (TCR) specificity. We and others (refs 5, 6 and M. Davis, personal communication) have taken an alternative approach. We have generated transgenic mice expressing the alpha beta antigen receptor from the cytotoxic T-lymphocyte clone 2C (ref. 7). In transgenic mice of the same haplotype as the 2C clone, the 2C TCR was expressed on 20-95% of peripheral T cells. Very few of these T cells carried the CD4 antigen; the vast majority were CD4-CD8+ and were able to lyse targets with the same specificity as the original 2C clone. These results indicate that the alpha beta heterodimer transfers specificity to recipient cells as expected from earlier studies, and that receptor specificity in T-cell repertoire selection is determined by both alpha beta heterodimer and CD4 or CD8 accessory molecules.

Animals↗

Binding of [3H]forskolin to solubilized preparations of adenylate cyclase.

The binding of [3H]forskolin to proteins solubilized from bovine brain membranes was studied by precipitating proteins with polyethylene glycol and separating [3H]forskolin bound to protein from free [3H]forskolin by rapid filtration. The Kd for [3H]forskolin binding to solubilized proteins was 14 nM which was similar to that for [3H]forskolin binding sites in membranes from rat brain and human platelets. Forskolin analogs competed for [3H]forskolin binding sites with the same rank potency in both brain membranes and in proteins solubilized from brain membranes. [3H]forskolin bound to proteins solubilized from membranes with a Bmax of 38 fmol/mg protein which increased to 94 fmol/mg protein when GppNHp was included in the binding assay. In contrast, GppNHp had no effect on [3H]forskolin binding to proteins solubilized from membranes preactivated with GppNHp. Solubilized adenylate cyclase from non-preactivated membranes had a basal activity of 130 pmol/mg/min which was increased 7-fold by GppNHp. In contrast, adenylate cyclase from preactivated membranes had a basal activity of 850 pmol/mg/min which was not stimulated by GppNHp or forskolin. Thus, the number of high affinity binding sites for [3H]forskolin in solubilized preparations correlated with the activation of adenylate cyclase by GppNHp via the guanine nucleotide binding protein (GS).

Adenylyl Cyclases↗

Germline organization of the murine T cell receptor beta-chain genes.

The complete germline organization of the beta-chain genes of the murine T cell receptor was elucidated in order to obtain the structural basis for understanding the mechanisms of somatic DNA rearrangements. Twenty of the 22 known variable (V beta) genes are clustered within 250 kilobases of DNA 5' to the constant region (C beta) genes. These V beta genes share the same transcriptional orientation as the diversity (D beta), joining (J beta), and C beta genes, which implies that chromosomal deletion is the mechanism for most V beta to D beta-J beta rearrangements. Within this V beta cluster, the distance between the most proximal V beta gene and the D beta-J beta-C beta cluster is 320 kilobases, as determined by field-inversion gel electrophoresis. The large distance between V beta and D beta, relative to that between D beta and J beta, may have significant implications for the ordered rearrangement of the T cell receptor beta-chain genes.

Animals↗

Beta-adrenergic responsiveness and cardiac autonomic receptors after implantation of the MtTW15 pituitary adenoma in the rat.

The effects of chronic MtTW15 pituitary adenoma implantation on beta-adrenergic responsiveness, cardiac beta-adrenoreceptors, and muscarinic receptors were studied in the rat. Five weeks after s.c. administration of tissue fragments of the MtTW15 adenoma, there was a 51 and 20% increase in the heart weight and body weight, respectively, and a 49-fold increase in the serum prolactin level as compared to the controls. At this time there was also an attenuation in the adenoma-bearing group of the ability of isoproterenol to produce a dipsogenic response and to increase the heart rate. In contrast, isoproterenol stimulated cardiac ornithine decarboxylase (ODC) activity 4.2-fold in both the control and adenoma-bearing groups. There was no change between the two groups in the cardiac ventricular beta-adrenoreceptor or muscarinic receptor concentration as measured by specific (-)-[125I]iodocyanopindolol (CYP) and (-)-[3H]quinuclidinyl benzilate (QNB) respectively. In addition, the concentrations of isoproterenol and carbachol required to inhibit by 50% (IC50) [125I]CYP and [3H]QNB binding, respectively, in the absence of 5'-guanylylimidodiphosphate (Gpp(NH)p) were not different between the two groups. In the presence of Gpp(NH)p, the isoproterenol IC50 value was not different between the two groups, whereas the carbachol IC50 value was increased slightly in the adenoma-bearing group. The data indicate that chronic MtTW15 adenoma implantation attenuated beta-mediated dipsogenic and heart rate responses but had little or no effect on cardiac ODC activity or cardiac autonomic receptor concentrations and agonist binding properties.

Adenoma↗

The recognition of facial expressions in the first two years of life: mechanisms of development.

In recent years the infant's ability to recognize facial expressions of emotion has attracted considerable attention from developmental psychologists. The rationale guiding much of this research has been that this ability plays an important role in later socioemotional development. In the present article, the research relating to this topic is reviewed and synthesized. It is concluded that the recognition of facial expressions develops slowly over the first 2 years of life, and that even at the end of the second year the infant's understanding of facial expressions is still quite rudimentary. Following this review is a discussion of 2 unresolved issues regarding the development of this ability. 1 issue relates to the biological/experimental basis on which the ability to recognize facial expressions develops. Research with primates is brought to bear on this point, and useful analogues with human infants are sought. From this research it is suggested that a component of the ability to recognize facial expressions is unlearned, although experience of some as yet undetermined nature affects this biological readiness. The second issue relates to the possible neurological mechanisms that mediate this ability. Research with primates, normal adults, and brain damaged adults is used to support the speculation that a posterior region of the right hemisphere is responsible for mediating the recognition of facial expressions.

Affect↗

Binding of [3H]forskolin to human platelet membranes. Regulation by guanyl-5'-yl imidodiphosphate, NaF, and prostaglandins E1 and D2.

[3H]Forskolin binds to human platelet membranes in the presence of 5 mM MgCl2 with a Bmax of 125 fmol/mg of protein and a Kd of 20 nM. The Bmax for [3H]forskolin binding is increased to 455 and 425 fmol/mg of protein in the presence of 100 microM guanyl-5'-yl imidodiphosphate (Gpp(NH)p) and 10 mM NaF, respectively. The increase in the Bmax for [3H]forskolin in the presence of Gpp(NH)p or NaF is not observed in the absence of MgCl2. The EC50 values for the increase in the number of binding sites for [3H]forskolin by Gpp(NH)p and NaF are 600 nM and 4 mM, respectively. The EC50 value for Gpp(NH)p to increase the number of [3H]forskolin binding sites is reduced to 35 mM and 150 nM in the presence of 50 microM PGE1 or PGD2, respectively. The increase in the number of [3H]forskolin binding sites observed in the presence of NaF is unaffected by prostaglandins. The binding of [3H]forskolin to membranes that are preincubated with Gpp(NH)p for 120 min or assayed in the presence of PGE1 reaches equilibrium within 15 min. In contrast, a slow linear increase in [3H]forskolin binding is observed over a period of 60 min when Gpp(NH)p and [3H]forskolin are added simultaneously to membranes. A slow linear increase in adenylate cyclase activity is also observed as a result of preincubating membranes with Gpp(NH)p. In human platelet membranes, agents that activate adenylate cyclase via the guanine nucleotide stimulatory protein (Ns) increase the number of binding sites for [3H]forskolin in a magnesium-dependent manner. This is consistent with the high affinity binding sites for [3H]forskolin being associated with the formation of an activated complex of the Ns protein and adenylate cyclase. This state of the adenylate cyclase may be representative of that formed by a synergistic combination of hormones and forskolin.

Alprostadil↗

Differential recovery of beta adrenoreceptor antagonist and agonist high affinity binding sites in the guinea-pig lung after irreversible blockade.

The recovery of guinea-pig lung beta adrenoreceptors and beta adrenergic-mediated airway responsiveness was studied after irreversible receptor blockade with bromoacetylalprenololmentane (BAAM). The antagonist receptor concentration and those receptors able to form the agonist high affinity binding state were determined by (-)-[3H]dihydroalprenolol (DHA) and [3H]hydroxybenzylisoproterenol (HBI) binding, respectively. Airway responsiveness was measured by the ability of isoproterenol infusions to shift the histamine dose-response curve for airway constriction. Twenty-four hours after a single i.p. injection of BAAM (20 mg/kg), both [3H]DHA and [3H]HBI binding were reduced by 48 to 51% without changing the KD value for either ligand. In addition, there was a complete block of airway responsiveness to isoproterenol infusion at 1 microgram/kg/min although responsiveness similar to control values was observed at a higher infusion rate (10 micrograms/kg/min). Ninety-six hours after BAAM treatment, [3H]DHA binding had recovered to the control value whereas no recovery of [3H]HBI binding or of airway responsiveness was observed. By 144 hr after injection, both [3H]HBI binding and airway responsiveness had recovered to control values. The data indicate that after irreversible blockade, the total receptor population as measured by antagonists recovers relatively quickly followed by a slower recovery of those receptors able to form the agonist high affinity binding state that parallels the recovery of airway responsiveness.

Adrenergic beta-Agonists↗

Electrophysiological correlates of infant recognition memory.

Event-Related Potentials were recorded from 6-month-old infants in order to examine the electrophysiological correlates of recognition memory. In 1 study, infants were shown 1 face briefly, followed by the same face presented with high probability, and a novel face presented with low probability. 2 components were observed that distinguished between the novel and familiar events. Differences between these components in latency, polarity, and scalp topography led to the suggestion that 2 processes were involved in recognizing the stimuli. In a second study infants were again presented with 1 face briefly, followed by the same face and a novel face presented with equal probability. 1 component at central scalp distinguished between the novel and familiar events. In a third study, infants were simply presented with 2 previously unseen faces equally often. Infants responded as if the faces were identical, suggesting that previous experience with 1 stimulus directs infants' attention to the novel stimulus during the test portion of the task. The extent to which the observed responses reflect the updating of working memory is discussed, as is the extent to which infants' electrophysiological response to stimulus novelty and uncertainty resembles the adult's.

Arousal↗

Regulation of [3H]forskolin binding to human platelet membranes by GppNHp, NaF, and prostaglandin E1.

Displaceable binding of [3H]forskolin to human platelet membranes can be detected in the presence of magnesium. There is an increase in the number of [3H]forskolin binding sites when membranes are incubated with GppNHp or NaF in the presence of magnesium. Prostaglandin E1, which stimulates human platelet adenylate cyclase, does not affect the binding of [3H]forskolin in the absence of GppNHp. However, the dose-response curve for the GppNHp-dependent increase in [3H]forskolin binding sites is shifted to lower concentrations in the presence of prostaglandin E1. Prostaglandin E1 potentiates the effect of GppNHp on [3H]forskolin binding most likely by facilitating the binding of the guanine nucleotide at the stimulatory quanine nucleotide regulatory protein of adenylate cyclase.

Alprostadil↗

Frequency and significance of delta antibody in acute and chronic hepatitis B. A United States experience.

Of 560 hepatitis B surface antigen-positive patients who were tested for antibody to hepatitis delta-antigen by blocking radioimmunoassay, 29 (5%) were seropositive. Patients with chronic active hepatitis had a greater frequency of seropositivity than those with chronic persistent hepatitis (26% vs. 0%, p less than 0.05), and patients with symptomatic chronic disease harbored the antibody more commonly than asymptomatic counterparts (14% vs. 2%, p less than 0.01) or patients with acute hepatitis (14% vs. 1%, p less than 0.02). Of 8 patients with acute fulminant hepatitis, including 6 who died of liver failure, none were seropositive. Antibody was detected in drug users, dialysis patients, hemophiliacs, and transfusion recipients; in 17 patients, however, including 3 homosexuals, it occurred sporadically. Samples harvested in 1969 contained delta-antibody. Antibody was found in most ethnic groups, including Orientals, where it occurred only in relocated Vietnamese. We conclude that delta-antibody is detected infrequently in a diverse referral population within the United States. Seropositivity is associated with symptomatic chronic disease and histologic findings of chronic active hepatitis. Homosexuals and resettled Vietnamese are susceptible to sporadic delta-infection.

Acute Disease↗

Intrametropolitan planning for community-based residential care: a goals programming approach.

Small community-based residential facilities have increasingly supplanted large-scale institutions as treatment settings for mentally and physically disabled, indigent, elderly and ex-offender populations in the United States. Because the intrametropolitan assignment of these service-dependent populations and their community care facilities has not been purposively planned, most facilities and clients have clustered in inner cities, resulting in the formation of service-dependent population ghettos. This paper outlines a goals programming approach to the client/facility assignment problem. The model provides a basis for an intrametropolitan distribution of residential service facilities that balances equity and efficiency goals and that protects both client and community rights. A regional fair-share plan that incorporates negotiation and arbitration techniques is offered as an institutional mechanism for implementing the goals programming framework.

Community-Institutional Relations↗

Age-related changes in cardiac muscarinic receptors: decreased ability of the receptor to form a high affinity agonist binding state.

Cardiac ventricular muscarinic cholinergic receptors and agonist binding properties were determined in Fischer 344 rats at 3, 12, and 24 months of age. Muscarinic receptors were determined by specific (-)-[3H]quinuclidinyl benzilate (QNB) binding, and the agonist binding properties were determined by competition assays. There were no differences in the concentration of the receptor or the dissociation constant of [3H]QNB binding among the three age groups. In cardiac membranes from 3- and 12-month-old animals, 5'-guanylyl-imidodiphosphate (Gpp(NH)p) increased by 16- to 18-fold (p less than .01) the concentration of carbachol required to inhibit [3H]QNB binding by 50% (IC50). At 24 months, however, Gpp(NH)p induced only a 2.7-fold shift in the carbachol IC50 value (p less than .01). The reduced shift was due to an increase in the carbachol IC50 value determined in the absence of Gpp(NH)p (p less than .01). There was no significant differences among the 3-, 12-, and 24-month-old animals in the half-maximal concentration of Gpp(NH)p required to produce the carbachol IC50 shift. The data indicated that with age there is a reduced ability of the muscarinic receptor to form a high affinity agonist binding state.

Aging↗

The generalized discrimination of facial expressions by seven-month-old infants.

2 experiments were conducted to examine 7-month-old infants' perception of the facial expressions happy and fear. Using a paired-comparison procedure, infants in the first experiment were able to generalize their discrimination of these 2 expressions across the faces of 4 male and female models if they were first presented with the set of happy faces, but not if they were first presented with the set of fear faces. A second experiment was conducted to examine the source of the stimulus presentation order effect. Here a second group of 7-month-old infants was presented with a single male or female face posing both the happy and fear expressions simultaneously. The results revealed significantly longer looking to the fear face. This preference to look at fear faces is discussed, as are its implications for studies of expression recognition in general.

Facial Expression↗

The distribution of serum high density lipoprotein subfractions in non-human primates.

The ultracentrifugal flotation patterns in 1.2 g/ml solvent and ultracentrifugal gradient distribution of high density lipoproteins (HDL) from the primates--human, apes and monkeys--were determined, with emphasis on the gorilla species of apes and rhesus monkeys. Diets for non-human primates were commercial chow, which is low in cholesterol. Molecular weights and protein, cholesterol, phospholipid and triglyceride compositions of various density fractions were determined on human, gorilla and rhesus HDL. The HDL2/HDL3 ratio was determined from the two peaks observed upon flotation in high salt in the analytical ultracentrifuge. The HDL2 of all three species of apes--gorillas (Gorilla gorilla), chimpanzees (Pan troglodytes) and orangutans (Pongo pygmaeus)--was always greater than HDL3, while that of all six species of Old World monkeys--Rhesus (Macaca mulatta), sooty mangabeys (Cercocebus atys), cynomolgus (Macaca fascicularis), stumptails, (Macaca arctoides) patas (Erythrocebus patas) and African greens (Cercopithecus aethiops)--was less. In addition, the HDL3 concentration in five gorillas was about 15 mg/dl as cholesterol while the HDL2 concentration was 92 mg/dl, much lower and higher, respectively, than humans. HDL2 of gorillas was similar in density and molecular weight to that of humans. The distribution of densities in gorilla HDL was predominantly in HDL2, while rhesus HDL usually, but not always, was unimodal, having a density distribution similar in heterogeneity to human HDL3, but somewhat less dense (peaking at 1.109 vs. 1.129 g/ml). The molecular weight of rhesus HDL was about the same as human HDL3 in all three density subfractions and at the peak density.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗