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Biomedical subjects

L A Roberts

Publications and source records attributed to L A Roberts.

At least 37 records · Page 2Linked to original sources
PubMed1996

Changes in hippocampal gene expression associated with the induction of long-term potentiation.

The expression of four genes: zif/268, c-fos, tubulin and alpha Ca2+/calmodulin-dependent protein kinase II (alpha CAMKII) was studied following the induction of LTP in Schaffer collateral CA1 neurone synapses in rat hippocampal slices maintained in vitro. Levels of c-fos mRNA and tubulin (T26) mRNA in area CA1 were unchanged after induction of LTP, however, zif/268 and alpha CAMKII mRNA levels showed a significant increase compared to non-potentiated controls. It is possible, therefore, to measure changes in gene expression using in situ hybridisation following induction of LTP in vitro and these results strengthen the theory that zif/268 and alpha CAMKII are involved in some aspect of the induction or maintenance of hippocampal LTP.

Animals↗
PubMed1994

Densitometry of the radius using single and dual energy absorptiometry.

Though spinal and femoral measurements are typically preferred for evaluating skeletal density, an abundance of forearm data exists, primarily from single photon absorptiometry (SPA) devices. Most dual X-ray absorptiometry (DXA) scanners are capable of scanning the forearm and provide analysis tools to duplicate conventional SPA measurements. In this study, we have compared the radius density measurements from three commonly available densitometers: a Norland 278 SPA, a Lunar DPX-L, and a Hologic 1000/W. Radius bone mineral density (BMD) on the nondominant forearm was measured in 28 volunteers (21 women and 7 men) aged 24-78, with an average age of 51 +/- 17 years. Values were compared and regression relationships derived at corresponding measurement sites. SPA and DXA BMD values were found to be highly correlated (r = 0.99) with small standard errors (0.014 g/cm2-0.021 g/cm2), though significant absolute differences were observed at most measurement regions. Correlation slopes ranged from 0.85 to 1.04, with intercepts from 0.01 to 0.08 g/cm2. Using the resultant regression equations, SPA BMD values can be converted to DXA values with an expected error of roughly 3%. DXA BMD can also be interconverted between Lunar and Hologic with a similar expected error. In situations where this level of imprecision is acceptable, patient forearm measurements obtained on different systems can be interconverted.

Absorptiometry, Photon↗
PubMed1993

Human immune response to cationized proteins. I. Characterization of the in vitro response to cationized diphtheria toxoid.

Cationization of proteins, i.e., increasing net positive charge by the substitution of carboxyl groups with positively charged residues, has been reported to enhance protein immunogenicity in animal model systems. In the present study, we have investigated the effect of cationization on the in vitro cell-mediated immune response of human mononuclear cells to diphtheria toxoid. A series of cationized DT preparations were generated by covalent modification with ethylenediamine, with pIs ranging from 4.6 to > 9.3, and tested for their ability to induce proliferation of normal human peripheral blood mononuclear cells. Cationized DT (cDT) was found to induce an antigen-specific, augmented proliferative response, relative to native antigen, which was directly proportional to the degree of cationization. Further characterization of the response to cDT demonstrated that (1) proliferative responses could be detected considerably earlier, and typically at much lower antigen concentrations, than the response to native DT; (2) the response was dependent on HLA-DR; (3) production of a number of cytokines, sp. IL-1 beta, IL-2, and IFN-gamma, was also elevated in cDT-stimulated cultures; and (4) the enhanced proliferative response to cDT could be attributed to CD4+ helper T cells. These results demonstrate that cationization of proteins enhances the ability to generate a cell-mediated immune response in humans and suggest that cationization may have utility in the design of more effective carrier proteins for human vaccines.

CD4 Antigens↗
PubMed1993

Human immune response to cationized proteins. II. Characterization of interaction of cationized diphtheria toxoid with human mononuclear cells.

Cationized diphtheria toxoid (cDT) has previously been shown to be more effective than the native protein as an inducer of human antigen-specific T cell responses. In the present study, biotin-labeled antigen and flow cytometric analysis were used to examine the possibility that enhanced immunogenicity of cDT may be a consequence of preferential binding to antigen-presenting cells. Strong binding of cDT, relative to native antigen, was noted for both monocytes and B cells. Characteristics of binding were similar for both cell types, including rapid saturation, temperature independence, and inhibition by unlabeled cationized proteins. Although both B cells and monocytes bound cDT, only monocytes were effective in triggering T cell proliferation, possibly as a result of slow internalization of bound antigen by B cells. Definition of the target structures of cationized proteins may allow for the design of more efficient vaccines, which would be specifically targeted to antigen-presenting cells in vivo.

Antigen-Presenting Cells↗
PubMed1993

Reaction time during cocaine versus alcohol withdrawal: longitudinal measures of visual and auditory suppression.

Visual and auditory stimulus discrimination tasks, analogous to those used in the Reitan-Klove Sensory Perceptual Examination, were performed by 12 cocaine-dependent and 5 alcohol-dependent patients after 1 week, 3 weeks, and 3 months of verified abstinence. Sixteen control subjects, who were not substance-dependent, performed the same tasks after comparable intervals. During each task, either visual or auditory stimuli were presented in the left, in the right, or in both sensory fields. A simple key press was made to discriminate these conditions. Cocaine-dependent patients responded more slowly than control subjects during both tasks. The reaction-time slowing persisted across all three sessions, spanning a 3-month period of abstinence. There were no significant differences between the cocaine-dependent and control groups in response accuracy. In the context of other findings, these findings are interpreted as reflecting an enduring effect of prior cocaine dependence on motor as opposed to sensory functioning.

Acoustic Stimulation↗
PubMed1991

Morphological innervation pattern of the developing rabbit heart.

The morphological innervation pattern of developing fetal and neonatal rabbit hearts was delineated histochemically by a cholinesterase/silver procedure and immunohistochemically with the monoclonal antibody HNK1, an antibody which recognizes some cells derived from neuroectoderm. Cholinesterase-containing nerves appeared distally on the outflow tract by gestational day 15 (G15). Isolated cells with cholinesterase-stained fine processes were present near the base of the pulmonary trunk. HNK1 antibody stained the same nerves and ganglia revealed by the cholinesterase reaction and other nerves in the rabbit heart. It was used to confirm that cells with fine neuron-like processes were present before nerve ingrowth. The G14 heart contained many HNK1 staining cells in the right atrium, outflow, and inflow tracts; cells with fine processes were few but increased at G16. By G17, a plexus of interweaving nerves and associated cells began to form at the base of the pulmonary trunk. Fine nerves encircled the base of the aorta, and others crossed the intercaval region dorsally. At G19, nerves 1) extended downward from a rich "bulbar" plexus along the front ventricular surface, 2) grew near the epicardial surface at the base of the heart along the atrial floor and ventricular roof, 3) traversed the vena cavae and intercaval region to enter the atrial roof, and 4) crossed the coronary sinus to reach the back ventricular walls. By G23, cholinesterase-staining nerves and ganglia in the atria and, epicardially, in the ventricles formed the general innervation pattern of the newborn and adult rabbit heart.

Animals↗
PubMed1991

The sinoatrial ring bundle: a cardiac neural communication system?

The sinoatrial ring bundle (SARB), was originally described as a "whitish bundle of tissue which describes an almost complete loop around the two venae cavae and the coronary sinus" in the adult rabbit heart (Paes de Carvalho et al., 1959). The histologically and electrophysiologically differentiated structure, derived from the embryonic venous valves, was suitably placed for rapid conduction from sinoatrial (SA) to atrioventricular (AV) node, but no evidence was found for this role. Today, the function of the SARB remains obscure. Cholinesterase/silver staining reveals the neural pattern associated with the SARB and suggests a function. Throughout its extent, the SARB contains a bundle of parallel muscle fibers and accompanying long nerves. The nerves distribute to structures at either side of the loop: superolaterally to pectinate muscle and inferomedially to the region of the AV node. Along the curve of the right SARB, the nerves contribute to a dense neural plexus with nerves coiled around muscle. The plexus communicates with the nearby SA node and with the ganglia inferior to the node near the inferior vena cava. The morphological pattern of neural elements is suitably organized to suggest tension monitoring and internodal, neural communication.

Animals↗
PubMed1990

An Australia-wide epidemic of Pseudomonas pickettii bacteraemia due to contaminated "sterile" water for injection.

Nineteen cases of Pseudomonas pickettii bacteraemia and one case of Pseudomonas cepacia bacteraemia were identified in an Australia-wide outbreak of nosocomial sepsis associated with contaminated water for injection. The contamination was limited to one batch of commercially produced water for injection. Four different organisms were identified (three biotypes of P. pickettii and one of P. cepacia). However, P. pickettii biotype 1 appeared to be relatively more virulent than the other biotypes as it was the only identified organism in blood cultures in nearly all cases of sepsis. The ampoules of "sterile" water were each contaminated with approximately 10(3) organisms per millilitre. The lack of an Australian central reporting system for bacteraemia delayed the recognition of this outbreak.

Adult↗
PubMed1989

Morphological study of the innervation pattern of the rabbit sinoatrial node.

The pattern of nerves, ganglia, and fine nerve processes in the adult rabbit sinoatrial node, identified by microelectrode recording, was defined by staining histochemically for cholinesterase followed by silver impregnation. A generalized repeatable pattern of innervation was recognized, including 1) a large ganglionic complex inferior to the sinoatrial node; 2) two or three moderately large nerves traversing the sinoatrial node parallel to the crista terminalis; 3) nerves entering the region from the atrial septum, the superior vena cava, and the inferior vena cava; and 4) a fine network of nerve processes, particularly extensive in the morphologically dense small-cell part of the sinoatrial node. When the site of initial depolarization in the node was located and marked by a broken-off electrode tip, it was found, after cholinesterase staining, to be characterized by a cluster of cells enclosed in a nest or basket of fine nerves. Similar nested cell clusters were observed elsewhere in the sinoatrial node in this same preparation and in other hearts. A complex interweaving of atrial muscle fibers was observed medial and inferomedial to the sinoatrial node, which may form the anatomical basis for the lack of conduction through this region. The morphological pattern of nerves, ganglia, and myocardial cells described in this study emphasizes the complexity of innervation of the sinoatrial node, including its intrinsic neural elements. Cholinesterase/silver staining can be useful in the definition and comparison of electrophysiologically identified sites within the sinoatrial node.

Animals↗
PubMed1988

Effects of hemoglobin perfusion on contractile function of the isolated ventricular septa.

Effects of three unmodified hemoglobin solutions on myocardial contractile function was evaluated using isolated perfused rabbit interventricular septa. The hemoglobin solutions tested were: a human hemoglobin solution (SFHS-A), a bovine hemoglobin prepared by a column chromatography (SFHS-B), and a bovine hemoglobin obtained by a ultrafiltration method (SFHS-C). Myocardial effects were assessed by comparing contractile parameters; developed tension (DT), resting tension (RT), and perfusion pressure (PP), measured before (control perfusion with Tyrode buffer) and during hemoglobin perfusion. Further, to examine the effects of hemoglobin solutions on myocardial contractility following a period of impaired flow, septal responses to a 10-minute period of ischemia (stopflow) were also studied. After a 10-minute perfusion with hemoglobin solution, SFHS-C increased DT to 124 +/- 12% (paired t-test, p less than 0.05) without causing a significant increase in RT or PP while SFHS-A and SFHS-B decreased DT to 96 +/- 20% (p greater than 0.05) and to 77 +/- 7% (p less than 0.05), respectively. A significant rise in PP (40-50% above baseline) was also noted with these solutions (p less than 0.05). Similarly, after a 30-minute reperfusion following a 10-minute ischemia, SFHS-C allowed significantly better percentage recovery (95 +/- 3%) than septa perfused with SFHS-A (81 +/- 2%) or SFHS-B (63 +/- 6%) (Student's t-test, p less than 0.05). These results indicate that hemoglobin solution, if properly prepared, does not seem to have acute deleterious effects on contractile function of the isolated heart.

Animals↗
PubMed1988

The positive chronotropic effect of acetylcholine has muscarinic and nicotinic components in the neonatal rat heart.

Acetylcholine increases ventricular automaticity in neonatal but not adult canine Purkinje fibers. In this study, we used a rat model to investigate the mechanism for the increased automaticity, and used surface electrodes to record spontaneous rates from the ventricular septa of three different age groups: 1 to 2 days old (neonates), 6 to 9 days old (1 week old) and adults. Acetylcholine, 10(-12) and 10(-11) M, induced a significant increase in automaticity from a control of 103 +/- 6.5 beats per min to 117 +/- 9.0 and 118 +/- 10.8 beats per min, respectively, in the neonates (P less than .05). The increase was attenuated by atropine, 2 x 10(-6) M (P = .05), and eliminated by propranolol, 2 x 10(-7) M, or hexamethonium, 5 x 10(-6) M (P less than .05). In 1-week-old rats, acetylcholine, 10(-12) M, induced a lesser increase in automaticity from a control of 106 +/- 13.0 to 113 +/- 14.0 beats per min (P less than .05). The increase was blocked by atropine, 2 x 10(-6) M, propranolol, 2 x 10(-7) M, and by hexamethonium, 5 x 10(-6) M (all P less than .05). In adults, acetylcholine did not increase automaticity. Among the neonatal septa, 82% showed increased automaticity with acetylcholine alone, 78% showed increased automaticity in the presence of atropine and 13% showed increased automaticity in the presence of either propranolol or hexamethonium, suggesting a largely nicotinic mediated and catecholamine dependent component. In 1-week-old septa, 75% showed increased automaticity with acetylcholine alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1987

Speech perception by four single-channel cochlear implant users.

Four profoundly deaf adults, each a recent recipient of a scala tympani implant, underwent auditory and auditory-visual speech comprehension evaluations. Two subjects had multiple-electrode auditory prostheses, and 2 had single-electrode implants. All subjects were tested preoperatively with a high-power hearing aid, and postoperatively with a single-channel wearable sound processor. Reported here are the results of the first formal speech recognition tests which were conducted during the 8 months after the sound processor fitting. Three subjects had used the single-channel processor on a daily basis for up to 8 months at the time of postoperative testing. The 4th subject was a nonuser. On listening tests, a comparison between pre- and post-implant scores revealed little difference for any subject. On postoperative speechreading tasks, all subjects identified medial consonant phonemes and 2-digit numerals better with stimulation than without. The 3 frequent users of the device experienced significant improvement on connected-discourse tracking, and their speechreading of videotaped and live voice CID Everyday Sentences (Davis & Silverman, 1978) was enhanced with the addition of stimulation. The nonuser was a very proficient speechreader at the outset and exhibited no significant difference on connected-discourse tracking with and without stimulation. Moreover her ability to speechread Everyday Sentences was hampered slightly by the addition of stimulation. This single-channel sound processor functioned as a sensory supplement for the 3 frequent users, but no subject was able to use the processor as a sensory substitute.

Adult↗
PubMed1986

Nociceptive responses to altered GABAergic activity at the spinal cord.

GABA agonists and antagonists were injected intrathecally at the spinal cord, to determine their effect on nociceptive thresholds. Tactile stimulation, applied against the flank by a medium diameter von Frey fiber (5.5 g force), elicited distress vocalizations after, but not before injection of the GABA antagonists, bicuculline MI or picrotoxin (0.25 and 1 microgram dosages). Vocalization threshold to tail shock was significantly reduced by bicuculline MI or picrotoxin. Tail flick withdrawal latency from radiant heat was not altered by GABA antagonists. The GABA agonist, muscimol, significantly elevated vocalization threshold to tail shock at a 5 micrograms dose. At a lower dose level (1 microgram), muscimol significantly reduced vocalization threshold to tail shock. Tail flick latency was significantly prolonged by the 5 micrograms dose of muscimol; however, flaccid paralysis of the hind limbs was also evident. Nociceptive thresholds were not altered by GABA or saline injection. These findings indicate that GABAergic activity contributes to the tonic modulation of nociception at the spinal cord.

Animals↗
PubMed1985

Hyperalgesia induced by altered glycinergic activity at the spinal cord.

Glycine or its receptor antagonist, strychnine, were administered perispinally to investigate their effect on nociceptive responses elicited by activation of various cutaneous receptors. Strychnine produced dose-dependent sensory and motor disturbances; 1 and 5 micrograms doses were sub-convulsive, eliciting recurrent episodes of coordinated grooming, scratching and biting at the skin, which persisted for approximately 10 minutes post-injection; higher doses (25 and 100 micrograms) increased the intensity and duration of these effects, and produced convulsive motor seizures. Motor disturbances were not elicited by glycine (5, 25, 100 and 400 micrograms). Strychnine treated rats, at all doses, vocalized consistently in response to light cutaneous stimulation; a significant proportion of glycine treated rats also vocalized, but were not as sensitive to mild stimulation. Skin hyperalgesia persisted for at least 30 minutes in both strychnine and glycine treated rats. Both strychnine and glycine significantly reduced vocalization thresholds to tail shock. However, no clear effect on tail flick latency was observed following either strychnine or glycine. These results indicate that glycinergic neurons contribute to the tonic regulation of nociceptive input at the spinal cord.

Animals↗
PubMed1985

Strychnine antagonizes vaginal stimulation-produced analgesia at the spinal cord.

Vaginal-cervical mechanostimulation (VS) suppresses vocalization and withdrawal responses to noxious stimulation. To determine whether the inhibitory neurotransmitter, glycine, contributes to the action of VS, strychnine, a specific glycine receptor antagonist was administered perispinally via intrathecal catheter in dosages of 1,5,25 and 100 micrograms. Prior to strychnine administration, VS (400 g force) elevated thresholds to elicit vocalization in response to graded intensities of tail shock, and blocked vocalization elicited by stimulation of a skin area, previously sensitized by intradermal injection of a 20% yeast solution. After strychnine administration the analgesic effects of VS were significantly attenuated. These findings suggest that the analgesic action of VS is partially mediated by glycine at the spinal level.

Analgesia↗