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Biomedical subjects

J E Robinson

Publications and source records attributed to J E Robinson.

At least 55 records · Page 3Linked to original sources
PubMed1996

Reproducibility of the circadian blood pressure fall at night in healthy young volunteers.

The aim of this study was to evaluate the reproducibility of the circadian blood pressure (BP) change in normal healthy volunteers. The subjects were 32 healthy, young, normotensive volunteers who underwent 24 h ambulatory BP monitoring on two occasions, at least 4 weeks apart. Data were analysed using standard definitions of day and night (i.e. 07.00-22.00 for daytime and 22.00-07.00 for night time), event diaries to identify individual's day and night time and a time independent method (cusum analysis). Intraindividual variations of BP were assessed using the coefficient of variation (CV). The mean 24 h BP was very reproducible with a CV of 4.7%. Using the fixed definition of day and night, mean night time systolic blood pressure (SBP) was significantly reduced on the second visit compared to the first (P < 0.001). Using fixed times for day and night, day-night difference was poorly reproducible, with a CV of 52% for SBP and 59% for diastolic blood pressure (DBP), however this improved using diary based day-night to 40/41% and cusum analysis to 24.6/28.1%. We recommend that circadian BP changes are studied using individual definitions of day and night or time independent methods such as cusum analysis.

Adult↗
PubMed1995

Ketorolac (Toradol) and acute random-pattern skin flap survival in rat.

OBJECTIVE: To assess the efficacy of sustained postoperative intramuscular ketorolac tromethamine (Toradol) at analgesic levels in the augmentation of acute, random-pattern skin flaps in rat. DESIGN: Prospective, randomized, placebo-controlled, animal trial. SETTING: Animal research laboratory, School of Medicine, Oregon Health Sciences University, Portland. SUBJECTS: Forty-four adult male Sprague-Dawley rats (260 to 280 g). INTERVENTIONS: Twenty-two treatment animals underwent modified McFarlane random-pattern skin flaps followed immediately by intramuscular loading doses of ketorolac. Treatment animals were then maintained on a regimen of intramuscular ketorolac using a three times a day dosing schedule for 14 days postoperatively. Twenty-two control animals underwent identical modified McFarlane random-pattern skin flaps and were given equivalent volumes of intramuscular saline on the same dosing schedule for the 14-day treatment period. MAIN OUTCOME MEASURES: Postmortem measurements of skin flap ischemia (expressed as a percentage of total flap surface area) were performed for both treatment and control animals by three independent, non-blinded observers using the acetate tracing technique. Both pooled and individual data were statistically analyzed using personal computer software. RESULTS: Forty-three of the 44 animals successfully completed the experimental trial. One animal in the treatment group died on postoperative day 3 of unknown causes. During the study period, one postoperative hematoma was detected in both the treatment and control groups. The mean percentage of skin flap ischemic necrosis observed in control animals (35.4%) was consistently less than that measured in the treatment group (36.4%). However, the difference in ischemic flap necrosis between control and treatment groups was not statistically significant (P = .6919). CONCLUSIONS: Comparatively high-dose intramuscular ketorolac failed to augment acute, random-pattern skin flap survival in rat when initiated in the immediate postoperative period. Complications of prolonged, intramuscular ketorolac were not observed in this trial. Further studies using preoperative initiation of drug therapy may help to clarify the true efficacy of ketorolac in flap augmentation.

Analgesics↗
PubMed1995

Semiautomated quantitation of urinary protein and creatinine.

The application of personal computers to routine tasks such as the recording and manipulation of data can greatly increase the speed and accuracy of the analyses. This report describes the use of a Macintosh computer and a BioTek microplate reader for the analysis of urinary protein and creatinine. Previously published assay methods for protein and creatinine were adapted for analysis using 96-well microplates. The adapted assays had excellent linearity (r2 = 0.99), with reduced variability compared to the previous methods. This resulted in increased sensitivity as demonstrated by 95% confidence limits. In addition, reductions of both assay materials and sample sizes were realized. The direct connection of the computer and microplate reader reduced the time needed to record absorbance measurements and perform analyses when compared to the more common protocols and methods of analysis. The assay protocols, equipment and interface, data file management, and methods of analysis are described.

Albuminuria↗
PubMed1995

Microdialysis: a novel tool for research in the reproductive system.

The technique of microdialysis has been applied extensively in neurobiological research. However, its potential as a tool for research in tissues other than the brain has not been fully explored. This article describes some of the situations in which microdialysis has been employed for studies in reproductive physiology and behavior. The examples have been chosen to give the reader a sense of the potential of the technique, its strengths, and some of its limitations.

Animals↗
PubMed1995

Is the inhibitory action of estradiol on luteinizing hormone pulse frequency in anestrous ewes mediated by noradrenergic neurons in the preoptic area?

This study tested the hypothesis that estradiol inhibits luteinizing hormone (LH) pulse frequency in anestrous ewes by increasing the activity of an inhibitory noradrenergic (NE) system that acts in the ovine preoptic area (POA). The effects of estradiol on the release of NE and other neurotransmitters in the POA were determined using intracranial microdialysis. Microdialysis probes (5 mm membrane length) were inserted via chronic guide tubes into the POA. Ringer's solution was pumped through the probes at a rate of 2 microliters/min for 8 h, the alpha-adrenergic antagonist phenoxybenzamine (PBZ; 60 micrograms/ml of Ringer's solution) was then administered via the probe from hours 8 to 12, and Ringer's solution alone was given the last 4 h. The outflow from the dialysis probes was collected every 20 min from 2 to 16 h and concentrations of aminergic transmitters and gamma aminobutyric acid determined by high-performance liquid chromatography. Blood samples were collected every 10 min throughout the experiment and the LH pulse patterns determined. Dialysis was done in the same neural area twice in each ewe, without (ovariectomy only) and with estradiol treatment (ovariectomy and a 1.5-cm-long Silastic capsule filled with crystalline estradiol placed subcutaneously for 2 days); the order of dialysis was randomized. As expected, estradiol decreased the LH pulse frequency. This negative feedback action of estradiol was associated with a decrease in mean NE concentrations in dialysate samples and an increase in the intra-animal variability of NE. Estradiol had no effect on any other neurotransmitter measured.(ABSTRACT TRUNCATED AT 250 WORDS)

Anestrus↗
PubMed1995

Melatonin-binding sites in the gonadotroph-enriched zona tuberalis of ewes.

The presence of melatonin-binding sites in the ovine pars tuberalis is well established, but data on melatonin binding in the pars distalis are inconsistent. The distribution of melatonin-binding sites in the ovine hypophysis was investigated using in vitro autoradiography and the high-affinity, high specific-activity ligand 2-[125I]iodomelatonin. The histology of sections was visualized with Heidenhain's azan stain and sections were immunoreacted against ovine LH (beta-subunit) using standard immunocytochemical techniques. Melatonin binding in the hypophysis was restricted to the pars tuberalis and the zona tuberalis. The zona tuberalis is histologically similar to the pars tuberalis and appears to be a ventral extension of this region, although the shape and size of the zona tuberalis are extremely variable between individuals. Like the anteroventral pars tuberalis, there is a high concentration of immunoreactive gonadotrophs in the zona tuberalis. The density of immunoreactive gonadotrophs alone is sufficient to discriminate between the zona tuberalis and the pars distalis. Our data suggest that the zona tuberalis and the pars tuberalis are part of the same endocrine tissue and that melatonin-binding sites are not present in the pars distalis proper.

Animals↗
PubMed1995

Gamma amino-butyric acid and the control of GnRH secretion in sheep.

The release of GnRH from nerve terminals in the median eminence into the portal vessels is influenced by factors in the internal and external environment of the animal. In the former category are the gonadal steroid hormones oestrogen and progesterone which alter the characteristics of GnRH secretion during the oestrous and seasonal cycles. These cannot exert their actions directly on the GnRH neurones as they do not possess hormone receptors. Therefore, some other steroid-sensitive neuronal system must relay this information to the GnRH neurones. Gamma amino-butyric acid (GABA) neurones are good candidates for this role as they contain steroid hormone receptors and synapse on GnRH neurones. Recent studies in ewes have sought to identify a role for GABA in mediating the actions of both oestrogen and progesterone on GnRH release. The technique of microdialysis was used to monitor GABA concentrations in areas containing GnRH cell bodies during the oestrogen-induced surge of GnRH and during progesterone negative feedback. Concentrations of this inhibitory neurotransmitter have been shown to fall in the former situation where GnRH release is being stimulated, but to be increased when progesterone is depressing GnRH release. GABA may also be important in mediating the seasonal switch in the negative feedback actions of oestradiol. During the anoestrous season, when oestradiol is a potent inhibitor of GnRH secretion, specific GABA receptor antagonists can stimulate neurohormone release, an action that is not observed in the breeding season when oestrogen is much less potent.

Animals↗
PubMed1994

Modelling the luteinizing hormone-releasing hormone pulse generator.

Pituitary hormones are released in pulses as a result of episodic patterns of electrical activity in neuroendocrine neurons. The mechanisms underlying such pulsatility have, however, been difficult to elucidate. For example, the luteinizing hormone-releasing hormone neurons regulating reproductive functioning have a sparse and scattered distribution within the hypothalamus which has made definitive electrophysiological investigation impracticable. Little is known not only of their electrical characteristics, but also of the critical neural components with which they interact to form the so-called "luteinizing hormone-releasing hormone pulse generator". We have used here a neural modelling approach, based on the FitzHugh-Nagumo model of a single neuron, to provide a simple dynamical network model of this neuroendocrine pulse generator. We have found that the minimal components required to generate pulsatile luteinizing hormone secretion arise from combining luteinizing hormone-releasing hormone neurons with reciprocally connected inhibitory interneurons and an external stimulatory input. Local GABA neurons and ascending noradrenergic and/or adrenergic inputs have been used as the biological basis for these respective components. The network displays a wide repertoire of behaviours comparable with experimental observations, including some thought previously to be paradoxical. The capacity of this model network to display complex behavioural features interpretable against experimental evidence suggests that this type of modelling may become a necessary adjunct to empirical studies of pulsatile neuroendocrine systems.

Action Potentials↗
PubMed1994

Complement C3, eosinophil cationic protein and symptom evaluation in interstitial cystitis.

Interstitial cystitis is a painful, irritative voiding dysfunction of unknown etiology. In this study 19 women undergoing treatment for interstitial cystitis and 6 healthy women of similar age provided 2 urine and serum specimens with at least a 3-month interval between collections. Complement C3 and eosinophil cationic protein were determined by immunoassay methods, and symptom severity was quantitated with a visual analog scale questionnaire. Concentrations of complement C3 and eosinophil cationic protein from either serum or urine were not significantly different between interstitial cystitis patients and controls at either determination, although substantial differences were noted even between individual initial and followup determinations. Normalization of urine osmolality did not alter these results. Symptom severity scores were significantly greater in interstitial cystitis patients compared to controls but failed to correlate with the concentrations of complement C3 or eosinophil cationic protein. Therefore, the hypothesis that complement C3 and eosinophil cationic protein may be etiological factors of interstitial cystitis is not supported.

Adult↗
PubMed1993

Calcitonin gene-related peptide (CGRP): immunocytochemical identification of a neuropeptide synthesised by ventral paraventricular magnocellular neurones in the sheep.

The distribution of calcitonin gene-related peptide (CGRP)-immunoreactive neurones was examined in the hypothalamus and pituitary gland of the short-term ovariectomised ewe. A large number of magnocellular CGRP-immunoreactive neurones were identified in the ventral paraventricular nuclei (PVN); few were found in the dorsal PVN and supraoptic nuclei. Parvicellular CGRP-immunoreactive neurones were identified in low density scattered throughout the preoptic region, anterior and basal hypothalamus and region of the stria terminalis. A dense CGRP innervation of the median eminence and neural lobe of the pituitary was observed. These observations reveal substantial species differences in CGRP immunoreactivity compared with the rat and show that magnocellular CGRP-synthesising neurones in the sheep are essentially restricted to, and define, the ventral PVN. This suggests a functionally distinct role for this previously neglected division of the PVN within the ovine hypothalamo-neurohypophyseal system.

Animals↗
PubMed1993

Antigenic variation in gp120s from molecular clones of HIV-1 LAI.

To address the relationship between primary sequence variation in HIV-1 gp120 and its antigenic structure in a simple system, we have measured the binding of human and murine monoclonal antibodies (MAbs) to gp120 from four molecular clones of HIV-1 LAI: HxB2, HxB3, Hx10, and NL4-3. Despite the close relationship between these clones, and their relatively conserved gp120 sequences, there is considerable variation in their antigenic structure, judged by MAb reactivities to the V2, V3, and C4 domains and to discontinuous epitopes. Because of our prior studies of the determinants of MAb binding to HxB2 gp120, we can make reasonable estimates of how sequence variation among the LAI clone gp120s affects their binding of some MAbs; for other MAbs our current knowledge of gp120 structure is too limited to allow such estimates. These results indicate that small variations in primary gp120 amino acid sequence can profoundly affect recognition of this glycoprotein by all five groups of defined anti-gp120 neutralizing antibodies.

Amino Acid Sequence↗
PubMed1993

Epithelium-free area in the thymic cortex of rats.

The histology of epithelium-free areas in the subcapsular region of the thymus was studied in Wistar rats. Lymphocytes in these areas were CD4/CD8 double-positive, TCR alpha/beta positive in low intensity, and in CD5 labeling either negative or positive in low intensity. There was a high proliferative activity as assessed by bromodeoxyuridine incorporation in vivo and detected by immunohistochemistry. Various macrophage types were observed. They were either large and round to slightly dendritic, or small and dendritic. Most large cells were positive for MHC Class II, and labeled by the antimacrophage antibodies ED1 and ED2. A few cells were strongly positive for Sudan black, Oil red O, nonspecific esterase, and acid phosphatase; they resembled the large rounded macrophages in the corticomedullary zone, although their MHC Class II and ED2 staining was more intense. A few cells showed features of tangible body macrophages, as they contained cellular debris. Serial sections showed that epithelium-free areas run from the subcapsular area to deep in the cortex, and often border the medulla. This opens the opportunity for immature lymphocytes to move into the medulla and corticomedullary zone without contacting and potential selection with cortical stromal elements other than macrophages in the epithelium-free areas. In this case, the epithelium-free areas may offer a separate intrathymic pathway for T lymphocytes.

Animals↗
PubMed1993

Distribution of estrogen receptor-immunoreactive cells in the preoptic area of the ewe: co-localization with glutamic acid decarboxylase but not luteinizing hormone-releasing hormone.

Using immunocytochemical techniques we have examined the distribution of cells containing estrogen receptors (ERs) in the preoptic and anterior hypothalamic regions of short-term (1 week) ovariectomized ewes. Subsequent double-labelling experiments examined the co-localization patterns of ER and luteinizing hormone-releasing hormone (LHRH) or glutamic acid decarboxylase (GAD) immunoreactivities. ER-immunoreactive (-IR) cells were identified throughout the central and medial aspects of the preoptic area in a continuum which begins at the level of the organum vasculosum of the lamina terminalis and terminates in the caudal anterior hypothalamic area. A conspicuous sub-population of densely clustered ER-IR cells was identified within this distribution extending from the central region of the preoptic area into the bed nucleus of the stria terminalis. ER-IR cells were also identified in the ventrolateral septum and supraoptic nuclei. Double-labelling experiments showed that although rostral LHRH neurons were surrounded by ER-IR cells, they did not themselves possess ER immunoreactivity. In marked contrast, we estimate that approximately 40% of GAD-IR cells in the central aspect of the medial preoptic area are immunoreactive for the ER and that these cells account for nearly 30% of all ER-IR cells in this region. These results indicate that, in common with other species, LHRH neurons in the ewe do not possess ERs and suggest therefore, that these neurons are unlikely to be modulated directly by circulating estrogens. However, large numbers of adjacent GABA neurons possess ERs and may comprise a major neuronal population mediating gonadal steroid input to LHRH neurons.

Animals↗
PubMed1992

Distinction of human immunodeficiency virus type 1 neutralization and infection enhancement by human monoclonal antibodies to glycoprotein 120.

There is increasing evidence that sera from HIV-1-infected individuals contain antibodies that enhance infection by HIV-1 in vitro. Previous work has demonstrated that complement receptors on T lymphoid cells and Fc receptors for IgG (Fc gamma R) on monocytic cells are required for enhanced infection by antibody-complexed HIV-1. Characterization of such infection-enhancing antibodies is essential because immunogenic epitopes which induce enhancing antibodies should be excluded from HIV-1 vaccines. This study was conducted to identify enhancing antibodies involved in Fc R-mediated enhancement of HIV-1 infection employing IgG human monoclonal antibodies (HMAbs) reactive against gp120 of HIV-1, which were produced by B cell lines derived from an HIV-1-infected individual. A potent neutralizing HMAb N70-1.5e did not enhance infection by HIV-1 (IIIB and MN strains), whereas HMAb N70-2.3a mediated enhancement of HIV-1 infection, but had little neutralizing activity. A competition radio immunoassay demonstrated that the two antibodies bind to distinct epitopes. These results indicated that enhancing and neutralizing antibodies can be induced by different epitopes on gp120, suggesting the potential for development of safe vaccines against HIV-1 by exclusion of immunogenic epitopes for enhancing antibodies. We made attempts to identify the epitope on gp120 that is recognized by the enhancing antibody N70-2.3a by using recombinant HIV-1 proteins and found that the antibody binds to a conformational site of nonvariable sequences in the carboxyl half (aa 272-509) of gp120.

Animals↗
PubMed1991

Synchronization of the circannual reproductive rhythm of the ewe by discrete photoperiodic signals.

Although many species display endogenous circannual rhythms of biological activity that are synchronized by day length, the specific photoperiodic requirements for synchronizing such rhythms are not established for any species. We tested the hypothesis that the circannual reproductive rhythm of sheep can be synchronized by exposure to just one or two discrete blocks of photoperiodic information each year. Ewes were pinealectomized to prevent their ability to transduce photoperiodic information into altered reproductive neuroendocrine activity. During the 53/4 yr following pinealectomy, specific photoperiodic signals were restored for discrete periods of time via replacement of 24-h patterns of melatonin, the pineal hormone that transmits photic information to the reproductive neuroendocrine axis. The ewes were kept in a 12-mo photoycycle that alternated between short (8L:16D) and long (16L:8D) days every 6 mo and that was 6 mo out of phase with the geophysical year. Pineal-intact control ewes exhibited synchronous annual reproductive cycles. Noninfused pinealectomized control ewes did not exhibit synchronous cycles. Pinealectomized ewes infused with alternating 70-day blocks of short- and long-day patterns of melatonin every 6 mo for the first 21/2 yr of the experiment exhibited synchronous annual reproductive cycles that were 6 mo out of phase with those of ewes maintained outdoors. This synchrony persisted when the frequency of the melatonin treatment was reduced to just one 70-day block of a long-day pattern of melatonin each 365 days. Cycle period was 368 +/- 3 days; standard deviation of the date of onset of reproductive induction averaged only 3 days. Our study provides the first direct evidence that a single block of photoperiodic information a year can synchronize a circannual rhythm.

Animals↗
PubMed1991

Antibody-dependent cell-mediated cytotoxicity directed by a human monoclonal antibody reactive with gp120 of HIV-1.

We used a human monoclonal antibody (MAb; 15e) to identify an antibody-dependent cell-mediated cytotoxicity (ADCC) epitope on HIV-1 gp120. 15e has been shown to recognize a conformation-dependent epitope on gp120 which is important in both CD4 binding and neutralizing of HIV-1 infection. 15e binds to gp120 of HIV-1IIIB but not HIV-1RF. Using a standard ADCC assay, 15e was found to mediate ADCC against cells infected with HIV-1IIIB but not HIV-1RF. 15e did not mediate ADCC against cells with recombinant gp120 bound to surface CD4, indicating that 15e does not mediate innocent bystander ADCC against uninfected CD4 cells. To better define the 15e epitope, we performed ADCC against target cells infected with a vaccinia vector which expresses processed HIV-1IIIB gp160 from which the third variable region was deleted (amino acids, 312-328). MAb 15e efficiently mediated ADCC against cells expressing this altered form of gp120, indicating that this region is not contributing to the conformational epitope defined by 15e. 15e defines an important epitope in the human immune response to HIV-1 infection. Antibodies with 15e-like activity may be useful in immunoprophylaxis or immunotherapy of HIV-1 infection.

Antibodies, Monoclonal↗