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Biomedical subjects

M J Taylor

Publications and source records attributed to M J Taylor.

At least 145 records · Page 8Linked to original sources

Determinants of responsiveness in mothers of children with intraventricular hemorrhage.

Explored relationships between maternal responsiveness and parenting stress, family, medical, and demographic factors in mothers of children born prematurely at very low birth weights with intraventricular hemorrhage. Mothers of 82 2-year-olds completed self-report questionnaires and were observed interacting with their children in free play during a yearly assessment. Path analysis (LISREL) revealed that lower maternal responsiveness, measured by the Parent/Caregiver Involvement Scale, was associated with greater demographic disadvantage and with high parent-related stress on selected subscales of the Parenting Stress Index. Child-related parenting stress was not associated with responsiveness, and severity of the child's medical condition at birth was weakly related. Results are discussed in the context of this unique population, and relevant research and measurement issues.

Adaptation, Psychological↗

Presence and localization of tumor necrosis factor alpha in the corpus luteum of nonpregnant and pregnant pigs.

The objectives of this study were to determine whether tumor necrosis factor alpha (TNF alpha) is present in porcine corpus luteum (CL) and, if so, to ascertain which cells of the CL were associated with TNF alpha. The influence of the reproductive state of the animals on the amount or cellular localization of TNF alpha in the CL was also investigated. Western blot analysis demonstrated the presence of a 34-kDa immunoreactive TNF alpha-like protein in CL from nonpregnant and pregnant pigs. The intensity of TNF alpha immunostaining in bands observed in Western blots did not differ when luteal protein from nonpregnant pigs or from pregnant pigs was analyzed. Positive immunostaining for TNF alpha, determined by immunocytochemistry, was localized within endothelial cells of luteal sections. Positive immunocytochemical staining was recorded in all reproductive states examined except in CL that had undergone functional luteolysis (reduced progesterone concentration). A single-cell assay for TNF alpha secretion (a reverse hemolytic plaque assay) confirmed in vitro secretion of TNF alpha by a cell type in luteal tissue with a size and nuclear morphology similar to an endothelial cell. The presence of TNF alpha in the endothelial cells in functional CL is consistent with a role for TNF alpha in the regulation of vascular development of the CL in swine.

Animals↗

Accelerated clearance of Onchocerca microfilariae and resistance to reinfection in interleukin-4 gene knockout mice.

Immunity to Onchocerca microfilariae (mf) in mice is associated with CD4+ Th2 cells and is dependent on IL-5. In view of the role of IL-4 in the development of Th2 cells, we have utilized IL-4 gene knockout mice (IL-4-/-) to investigate microfilarial clearance and resistance to reinfection. Paradoxically, in the absence of IL-4 there is accelerated clearance of microfilariae during a primary infection and unimpeded expression of resistance to reinfection. IL-4-/- mice showed a lack of an IgE response although peripheral eosinophilia was equivalent to wildtype controls. The data presented here suggest that elimination of mf can occur independent of IL-4 and that in this model it may even be detrimental to the host.

Animals↗

Event-related potentials (ERPs) and intelligence in neonatally identified 47,XXY males.

The event-related potentials (ERPs) of 18 extra X males (mean age 18.1 years) were recorded during the course of phonemic and orthographic discrimination tasks. The N2 and P3 latencies and amplitudes of subjects were examined in relation to their verbal and nonverbal intelligence test scores based on assessments at three ages: prior to puberty, during puberty and at sexual maturity. The results indicated that verbal abilities at most test occasions were significantly related to P3 latencies. Nonverbal abilities were largely uncorrelated with ERPs. The findings suggest that the verbal deficits of extra X males are the result of unlateralized individual differences in neural cognitive processing.

Adolescent↗

Onchocerca volvulus larval antigen, OvB20, induces partial protection in a rodent model of onchocerciasis.

OvB20 is an antigen of Onchocerca volvulus preferentially recognized by sera from cattle vaccinated with irradiated infective larvae of Onchocerca lienalis. Antibodies raised against the recombinant protein were used to characterize the expression of the native protein in different developmental stages of O. volvulus and the rodent filaria Acanthocheilonema viteae. In O. volvulus, antibodies reacted to a polypeptide of 42 kDa in microfilariae and with proteins of 52 and 65 kDa in third-stage larvae. No products were detected in adult stages. Immunogold electron microscopy localized the native protein to discrete patches of the hypodermis and cuticle of infective larvae. Characterization of a homologous protein in A. viteae confirmed the stage-specific expression in infective larvae of the 65-kDa protein, which was secreted during in vitro culture. Vaccination of rodents against A. viteae with a B20-maltose-binding-protein fusion protein resulted in a 49 to 60% reduction in adult worm recoveries with a corresponding 97% reduction in microfilaremia.

Animals↗

The delivery of insulin from aqueous and non-aqueous reservoirs governed by a glucose sensitive gel membrane.

A self regulating delivery device, responsive to glucose, has been shown to operate successfully in vitro. This comprises a gel membrane which determines the delivery rate of insulin from a reservoir. The gel consists of a synthetic polysucrose and the lectin, concanavalin A. The mechanism is one of displacement of the branched polysaccharide from the lectin receptors by incoming glucose. The gel loses its high viscosity as a result but reforms on removal of glucose, thus providing the switch controlling the drug diffusion rate. The drug does not require to be chemically modified and thus the device is adaptable to other anti-hyperglycaemic drugs. However, results here indicate that the molecular weight of the solute may be an important parameter. Others include path length, gel formulation and temperature. It had been hypothesised that the reversal might be improved by the use of a non-aqueous reservoir of insulin. However, with the use of insulin, the switching off was found to be superior to that found with other test solutes used in previous studies, irrespective of the reservoir solvent. The advantages in the use of the non-aqueous system include, however, more reproducibility in the magnitude of response and a reduced temperature sensitivity.

Concanavalin A↗

Stimulus-independent thought depends on central executive resources.

Stimulus-independent thoughts (SITs) are streams of thoughts and images unrelated to immediate sensory input. Four experiments examined the contribution of aspects of working memory to production of SITs. In Experiments 1 and 2, interventions that were targeted on, respectively, phonological and visuospatial components of working memory both interfered with production of SITs, but there was evidence that these tasks also made demands on central executive resources. Experiments 3 and 4 specifically examined the hypothesis that production of SITs and control of nonproceduralized tasks both depend on central executive resources, and so should show mutual interference. In Experiment 3, prior practice on pursuit rotor and memory tasks reduced the interference with SITs from concurrent task performance. In Experiment 4, randomness within a task involving random-number generation was less when SITs were being produced concurrently than it was when they were not. The results suggest that production of SITs depends on central executive resources.

Adult↗

Permeation of rabbit common carotid arteries with dimethyl sulfoxide.

Proton nuclear magnetic resonance has been used to measure the kinetics of permeation of dimethyl sulfoxide in the common carotid artery of the rabbit. The process is described by the following exponential equations, where t = time in minutes: % Unexchanged at 2 degrees C = 70e-0.515t + 30e-0.104t and %Unexchanged at 22 degrees C = 70e-1.790t + 30e-0.146t. The times required for 95% equilibration were 13 min at 22 degrees C and 18 min at 2 degrees C. The corresponding times for 99% equilibration were 24 and 32 min, respectively.

Animals↗

Tumor necrosis factor involvement in the toxicity of TCDD: the role of endotoxin in the response.

We have previously demonstrated that tumor necrosis factor is involved in the acute toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), since therapies designed to attenuate the effects of tumor necrosis factor resulted in reduced mortality and toxicity in mice exposed to an LD75 dose of TCDD. The current study addresses whether endotoxin may be a contributing factor in the cachexia and mortality resulting from TCDD exposure. Endotoxin-nonresponsive C3H/HeJ mice and endotoxin-responsive C57BL/6 mice were treated with 350 micrograms/kg TCDD and body weight and mortality were recorded. C3H/HeJ mice showed no trend in body weight loss (p = 0.554), while C57BL/6 mice demonstrated a statistically significant (p < 0.01) linear decline in body weight of -0.23 g/day, resulting in a net loss of 3.5 g over 15 days preceding mortality. Mortality was observed in the C57BL/6 mice beginning on day 16 with 100% of the mice dying by the 23rd day while no mortality was observed in C3H/HeJ mice until the 24th day of the study with only 22% mortality observed. These data further demonstrate that endotoxin is a contributing factor to the cachexia and lethality of TCDD.

Animals↗

Evidence for a novel source of relaxin: atrial cardiocytes.

Antibody-directed, complement-induced erythrocyte lysis (reverse hemolytic plaque assay) around atrial cardiocytes was used to determine whether this cell type possesses the capacity to secrete the insulin-like hormone relaxin. After 2h of incubation, 33 +/- 4% (n = 3) of cardiocytes derived from the atria of neonatal rats secreted detectable amounts of immunoreactive relaxin (i.e. formed plaques) when cultured in monolayers. Increased culture time of cardiocytes failed to increase the fraction of cardiocytes that secreted relaxin. The cumulative amount of relaxin secreted after 3h of incubation (plaque area) was 31% greater (P < 0.05) than the amount of hormone present after 1h of incubation, evidence of sustained peptide secretion by cultured cardiocytes. These data suggest that the source of the endogenous ligand for the specific and high-affinity relaxin receptors located in rat atria is the atrial cardiocyte itself. Therefore, relaxin may act via autocrine and/or paracrine routes to regulate cardiovascular structure and/or function.

Animals↗

Protective immunity against Onchocerca volvulus and O. lienalis infective larvae in mice.

Acquired resistance to both Onchocerca volvulus and O. lienalis infective larvae, implanted within micropore chambers, could be induced in mice following immunization with irradiated L3 larvae. In experiments with O. volvulus in BALB/c and BALB/c. By mice, consistent levels of protection (61-75% reductions compared to challenge controls) were achieved with challenge infections of 2 week duration. In DBA/2 mice, levels of protection against O. lienalis were lower and more variable (42-63%): Moreover a 3 week period between challenge and recovery was required before significant reductions in larval recovery became detectable in vaccinated animals. Immunization of CBA or BALB/c mice with O. lienalis microfilariae, or CBA mice with normal or irradiated O. lienalis L3 larvae, failed to induce killing or growth retardation of developing larvae. Preliminary characterization of the effector mechanisms and cytokines associated with protective immunity against O. volvulus infective larvae revealed elevated levels of eosinophils in peripheral blood and within micropore chambers during challenge infections in vaccinated mice. Spleen cells from the same animals stimulated with parasite antigen induced significant levels of IL-5, IL-4 and IFN gamma. These cytokines were barely detectable in antigen stimulated cells from challenge control mice.

Animals↗

Lipopolysaccharide and a phorbol ester stimulate secretion of tumor necrosis factor-alpha from alveolar macrophages through action on overlapping subsets of cells.

A cell-by-cell analysis of the secretory ability of stimulated, individual alveolar macrophages (AMs) was performed through use of a tumor necrosis factor alpha (TNF-alpha) reverse hemolytic plaque assay. Two functional end points were measured: the percentage of AMs that were TNF-alpha secretors and the cumulative amount of TNF-alpha secreted by AMs (average plaque area, microns 2). Lipopolysaccharide (LPS; 100 micrograms/ml) increased cumulative TNF-alpha release at both 7 and 20 h of incubation. On the other hand, a phorbol ester (phorbol myristate acetate, PMA) stimulated TNF-alpha release at 20 h of incubation but not at 7 h. Under nonstimulated culture conditions, 5-10% of all AMs released detectable TNF-alpha PMA (but not LPS) induced a significant increase in the fraction of AMs capable of releasing TNF-alpha (15.1 +/- 1.1% vs. 9.0 +/- 1.6%, PMA vs. control, P < .05). Differences in the time course of secreted TNF-alpha, together with the recruiting effect of PMA, suggest that LPS and PMA target TNF-alpha-secretory subpopulations of AMs that differ in number and secretory characteristics.

Animals↗

The effect of polyvinylpyrrolidone and the cooling rate during corneal cryopreservation.

The effect upon endothelial cell survival of (a) PVP and (b) the cooling rate was investigated during the cryopreservation of rabbit corneas with 3 mol/liter dimethyl sulfoxide (Me2SO) dissolved in a hyperkalemic buffer vehicle solution that we designated CPTES; this solution was designed specifically to restrict deleterious ionic imbalances and cell swelling during hypothermic procedures. Polyvinylpyrrolidone (PVP) was used as the colloid and the corneas were cooled at 0.03, 0.1, 1, 25, or 125 degrees C/min, using the minimum amount of extracellular solution. Electron microscopy as well as staining with fluorescein diacetate and ethidium bromide (FDA/EB) was used to assess cellular integrity. To reduce osmotic stress, steps for the serial equilibration of the cryoprotectant additives (CPAs) were based upon calculations that predict endothelial volume during CPA exchange. A toxicity study showed that at 0 degrees C all the CPA equilibration protocols were well tolerated; for example, FDA/EB staining indicated that 97% intact cells were retained following direct transfer to 3 mol/liter Me2SO in CPTES to which 40% w/v PVP had been added as an osmotic buffer. However, less than 20% of cells were intact by FDA/EB staining with all corneas frozen at rates > 1 degree C/min regardless of which equilibration protocol was employed, nor were there any intact cells when 3 mol/liter Me2SO in CPTES was used alone at the lowest cooling rate. At intermediate cooling rates viability was improved: the highest mean survival of 81% was obtained using 3 mol/liter Me2SO in CPTES plus 40% PVP. Electron microscopy showed that detachment of the endothelial layer often occurred, but least damage was evident following exposure to 3 mol/liter Me2SO in CPTES plus 40% PVP and cooling at 1 degree C/min. No thawed cornea could maintain normal control of hydration immediately upon return to isotonic medium. The results show that, with these cryopreservation protocols, loss of cell integrity occurs at cooling rates greater than 1 degree C/min, whereas at lower rates higher survival of individual cells was achieved, but cellular adhesion to the basement membrane was impaired.

Animals↗

Effect of cooling rate and its interaction with pre-freeze and post-thaw tissue culture on the in vitro and in vivo function of cryopreserved pancreatic islets.

Rapid cooling destroys passenger lymphoid cells during cryopreservation. We now describe improved in vivo survival of rat islets after rapid cooling by adding pre-freeze tissue culture. Islets were equilibrated with 2M dimethylsulphoxide, cooled at 0.3 degrees, 20 degrees, or 70 degrees C/min, and stored at -196 degrees C. The culture was kept at 37 degrees C for 2 or 72 h before and/or after preservation. When cooled at 0.3 degrees C/min, keeping the culture for 72 h gave the highest proportion of dye-excluding cells, but more than 50% were viable under all culture conditions. Islets cooled at 20 degrees or 70 degrees C/min (rapidly) required 72 h of culture for a survival rate of more than 50%. When islets were cultured for 72 h before cryopreservation, their in vitro insulin secretory ability was similar to that of slowly cooled islets and they were able to sustain normoglycaemia in diabetic animals, although more islets were needed. Extended tissue culture before freezing improves the survival of rapidly cooled islets and is therefore important for combined immunomodulation and cryopreservation.

Animals↗

Effect of chlormethiazole, dizocilpine and pentobarbital on harmaline-induced increase of cerebellar cyclic GMP and tremor.

Administration to mice of harmaline (100 mg/kg SC) resulted in a greater than two-fold increase in cyclic GMP in the cerebellum 15 min later. This response was inhibited by pretreatment 5 min before the harmaline with pentobarbital (ED50 6.5 mg/kg), chlormethiazole (ED50 10.4 mg/kg) and dizocilpine (ED50 0.5 mg/kg). Harmaline-induced tremor was inhibited by pentobarbital (ED50 30 mg/kg) and chlormethiazole (ED50 50 mg/kg) but not dizocilpine. The data demonstrate that the harmaline-induced tremor and cerebellar cyclic GMP rise are probably not associated. They also demonstrate that chlormethiazole is able to inhibit a biochemical response (the increase in cerebellar cyclic GMP) which results from increased glutamate function.

Animals↗