Biomedical subjects

M J Taylor

Publications and source records attributed to M J Taylor.

At least 109 records · Page 6Linked to original sources

PubMed1998

Predictors of relapse in long-term abstinent alcoholics.

OBJECTIVE: The goals of this study were to examine the hazard of relapse during an average 11 years of follow-up in alcoholics who had achieved long-term abstinence and to determine predictors of later relapse. METHOD: Male alcoholics (N = 77) with at least 18 months of stable abstinence at time of entry were followed for 2 to 17 years (mean follow-up = 10.9 years). During follow-up, detailed information regarding relapse/abstinence and interim drinking behavior was recorded. Potential predictors of relapse collected at enrollment included past drinking history, severity of alcohol-related life problems, degree of neurocognitive impairment based on neuropsychological (NP) tests, psychological distress (MMPI) and past medical health. RESULTS: Twenty-four of 77 (31%) long-term abstainers relapsed during the follow-up period. The average annual hazard rate of relapse was 3.8% in the first 5 years of follow-up and 2.6% over the next 6-11 years. Based on Cox proportional hazard regression analyses, the only significant variables to predict relapse were MMPI Scale 4 (Psychopathic Deviate, relative risk = 3.16, 95% CI = 1.19-8.38) and prior history of alcohol-related life difficulty (i.e., citation for driving while intoxicated, relative risk = 2.64, 95% CI = 1.05-6.64) (chi2 = 14.2, 2 df, p < .001). CONCLUSIONS: There is approximately a 3% annual risk of relapse in alcoholics who have been able to achieve long-term abstinence, even after 5 years of abstinence. Alcoholics who resumed drinking had greater indicators of longer standing psychological trait disturbance, reflected in elevated MMPI Scale 4 and history of more alcohol-related social difficulties. Placing the present study in the context of previous research that focused primarily on predictors or relapse in the shorter term, it appears that, whereas mood disturbance predicts short-term outcome, more enduring personality traits predict long-term success in remaining abstinent.

Adult↗

PubMed1998

Cloning and expression of porcine recombinant soluble tumor necrosis factor receptor 1.

OBJECTIVE: To clone, sequence, and express porcine recombinant soluble tumor necrosis factor receptor 1 (sTNFR1). PROCEDURE: A polymerase chain reaction (PCR)-based library enrichment technique was used to isolate a fragment of porcine TNFR1. The mature extracellular domain of porcine TNFR1 was subcloned into an expression vector and expressed in Escherichia coli as a fusion protein. Protein product was purified by immunoaffinity chromatography, using a commercially available affinity gel specific for the marker peptide of the fusion protein. The bioactivity of the purified protein was tested for its ability to inhibit TNF-mediated cytotoxicity in a PK(15) bioassay. RESULTS: A 927-base pair fragment of porcine TNFR1 encoding the entire extracellular and transmembrane domains, as well as 75 amino acids of the cytoplasmic domain, was isolated from a porcine lung cDNA library. The extracellular domain was expressed as a soluble TNFR1 fusion protein with a yield of 120 to 150 microg/L of culture. Affinity-purified porcine sTNFR1 was able to inhibit TNF-mediated cytotoxicity of porcine PK(15) cells in dose-dependent manner. CONCLUSIONS: Porcine recombinant sTNFR1 inhibits TNF bioactivity in vitro. This recombinant protein will be useful for developing TNFR1 antibodies and studying the roles of TNF and TNFR1 in the pathogenesis of infectious diseases in swine.

Animals↗

PubMed1997

Normalizing the crossover effect: enhancement of cognitive attentional processing in schizophrenia.

Thirty male schizophrenic subjects and 20 male control subjects were administered both the classic Rodnick and Shakow reaction time (RT) procedure and a modified experimental procedure using a balanced design in an attempt to enhance cognitive attentional processing and inhibit the crossover effect in schizophrenic patients. The experimental procedure increased the number of predictable trials, provided more information about the task and presented the regular trials in a simple ascending order. Analysis of the RT data showed the typical early schizophrenic crossover and late normal crossover on the standard task, while schizophrenic patients in the experimental condition showed a new finding of statistically significant normalization of the early crossover effect. The results support Shakow's theory of attentional set deficit in schizophrenia and in conjunction with previous findings suggest that separate neuropsychological mechanisms of cognitive preparatory attention and a more automatic form of vigilance attention may, respectively, underlie the regular and irregular procedures of the traditional RT task.

Adolescent↗

PubMed1997

Gross damage accumulation on frozen rabbit liver due to mechanical stress at cryogenic temperatures.

The second phase of a pilot study dealing with the mechanical response of frozen biological tissues to external compressive load is presented. This stage deals with histological observations of the damage accompanying mechanically induced permanent deformation in frozen rabbit liver. no significant gross histological damage was observed in the liver samples due to either processing the tissue in the frozen state, due to slow cooling of the liver tissues down to -20 degrees C, or due to rapid cooling of the samples down to -196 degrees C. No histological changes were observed in tissue samples that were loaded within the elastic regime, that is, below the yield strength of the material. Therefore, it is concluded that histological changes due to mechanical stresses are associated with plastic (permanent) deformations. Histological observations indicate that linear cracks which appear to have no preferred orientation develop due to mechanical stress beyond the yield strength of the frozen tissue. These cracks accumulate until final failure of the frozen tissue, when the tissue sample collapses to rubble. Based on histological observations and concepts from solid mechanics, an interaction between crack formation and irregularities in the frozen medium is suggested. Significant sources for such irregularities, in an homogeneous tissue such as the liver, are blood vessels and bile ducts. These irregularities may either initiate crack formation or, on the other hand, may also arrest propagating cracks.

Animals↗

PubMed1997

Hyperplastic changes within the leptomeninges of the rat and monkey in response to chronic intracerebroventricular infusion of nerve growth factor.

Recombinant human nerve growth factor (rhNGF) was delivered for up to 6 months by continuous intracerebroventricular (i.c.v.) infusion to CD (Sprague-Dawley derived) rats and cynomolgus monkeys. Rats (n = 15/sex/group) received doses of 0 (vehicle), 6, 60, or 300 ng/day; monkeys (n = 5/sex/group) received 0, 0.6, 6, or 60 microg/day of rhNGF. Animals tolerated i.c.v. infusion with no behavioral signs attributable to rhNGF. Body weight was transiently decreased in female rats at the highest dose. At the completion of dosing, histological examination in both species revealed an increase in the thickness of the leptomeninges along the ventral and lateral surfaces of the hindbrain and extending over the dorsal aspect of the spinal cord. The change was present to varying degrees at all doses of rhNGF and tended to be more severe at higher doses. At the light microscopic level, the leptomeninges contained layers of well-differentiated, spindle-shaped cells and a plexus of axonal fibers. Cells were immunoreactive for S-100 protein and were associated with an accumulation of Type IV collagen, suggesting Schwann cell origin. Electron microscopy revealed numerous fine caliber axons ensheathed by the presumptive Schwann cells, with myelination of individual axonal segments. These findings suggest that chronic i.c.v. delivery of rhNGF has stimulated axonal sprouting and secondary hyperplasia of Schwann or Schwann-like support cells within the pia-arachnoid.

Animals↗

PubMed1997

Effects of methylphenidate in children with attention deficit hyperactivity disorder: a comparison of event-related potentials between medication responders and non-responders.

Event-related potentials (ERPs) were compared among three groups, each with 13 subjects: (1) ADHD non-responders to methylphenidate treatment; (2) ADHD responders to methylphenidate treatment; and (3) normal control children. Response to methylphenidate was determined through extensive psychoeducational and cognitive assessments during a 4-week double-blind medication assessment. ERPs were recorded each week from 13 active electrodes during a visual feature detection task and a semantic classification task. Significant group effects were found for N2 and P3b latencies due to longer latencies for the ADHD children. Off medication, there were no differences between responders and non-responders. However, on methylphenidate non-responders had significantly longer P3b latencies than responders. Cognitive testing also revealed differential performance on medication between non-responders and responders on the paired-associate learning (PAL) task. Thus, both cognitive and ERP measures were found to differentiate ADHD non-responders and responders to methylphenidate treatment.

Adolescent↗

PubMed1997

Magnetic immuno capture PCR assay (MIPA): detection of Leptospira borgpetersenii serovar hardjo.

Magnetic immuno PCR assay (MIPA) was developed for the rapid detection of leptospires excreted in urine samples (n = 59) collected from 35 experimentally infected cattle. The immunomagnetic separation of leptospires from inhibitors in frozen formalin fixed bovine urine prior to PCR detection resulted in a marked improvement on previous detection methods. MIPA is a rapid 5 step protocol requiring 70 mins preparation time prior to amplification, which consistently detects 10(1) organisms. MIPA detected 76% (38/50) of culture positive urines and in addition three urines that were culture negative were shown to be positive by this method of detection. Consequently we conclude that whilst MIPA is an improvement on previously published PCR detection methods, the culture of the organism is still the standard against which other detection methods have to be compared.

Animals↗

PubMed1997

Assessment of differential attention mechanisms in seizure disorders and schizophrenia.

This study examines differential attention deficits in 19 temporal lobe epilepsy (TLE) patients, 15 generalized seizure patients (GSP), and 19 schizophrenic patients, compared to 20 normal controls. All participants were tested on a variable foreperiod reaction time (RT) task and continuous performance test (CPT). Temporal lobe epilepsy patients and schizophrenic patients show crossover deficits on the RT task requiring a conscious, effortful, preparatory motor set; while GSP show impairments on the CPT requiring vigilant, self-directed attention to external stimuli. The results suggest separate cortical and subcortical brain systems in the respective attentional deficits and in the etiologies of TLE, GSP, and schizophrenic disorders.

Adult↗

PubMed1997

Assessment of brain function in adolescent anorexia nervosa before and after weight gain.

This study assessed brain function in 20 adolescent females with anorexia nervosa (AN) and 20 controls using event-related potentials (ERPs) and a battery of neuropsychological tests. In the AN group, N4 latencies for a nonverbal memory task were significantly longer than for a verbal task, and P3 latencies for the verbal task were significantly longer among anorexics as compared to controls. On the nonverbal task, the AN group failed to show a right > left hemispheric asymmetry for P3 amplitudes which was observed for controls. These group differences for P3 latency and amplitude were particularly pronounced in the central-parietal region of the head. Body Mass Index (BMI) in the anorexic group significantly predicted N4 amplitudes for the verbal task in the left hemisphere and P3 amplitudes for the nonverbal task in the right hemisphere. The two groups did not differ on any of the tests used to assess neuropsychological functioning. Eight nutritionally recovered patients and their matched controls were retested using the same procedures. Anorexics showed larger P3 amplitudes for the verbal as compared to the nonverbal task at follow-up. These findings provide evidence for localized brain dysfunction in anorexia nervosa that only partially normalizes with weight gain.

Adolescent↗

PubMed1997

Memory for verbal information in individuals with HIV-associated dementia complex. HNRC Group.

Patterns of memory performance were examined for 9 participants with HIV-associated dementia (HAD), 15 HIV-seropositive participants without dementia, and 15 HIV-seronegative controls. Episodic and semantic memory were assessed using the California Verbal Learning Test, the Boston Naming Test, and Verbal Fluency tests. The HAD group showed deficits in episodic memory, with relative sparing of semantic memory. In addition, results suggest a retrieval deficit in HAD rather than a deficit in retention of information. This pattern is consistent with the presence of a subcortical dementing process and supports findings from previous neuropathological, neuroimaging, and neuropsychological studies suggesting that subcortical brain dysfunction is frequently associated with HIV disease (e.g., Navia, Jordan, & Price, 1986).

AIDS Dementia Complex↗

PubMed1997

Protective responses against skin-dwelling microfilariae of Onchocerca lienalis in severe combined immunodeficient mice.

Inoculation of severe combined immunodeficient (SCID) mice with microfilariae of Onchocerca lienalis results in a sustained infection of the skin, extending for months beyond the point at which the parasites are eliminated from immunocompetent BALB/c controls. Reconstitution of SCID mice with spleen cells, thymocytes, or CD4+-cell-enriched splenocytes from naive BALB/c donors confers the ability to mount a protective immune response, leading to the rapid elimination of microfilariae. High levels of interleukin-5 and low levels of gamma interferon in the sera of reconstituted SCID mice during the destruction of microfilariae suggest that this protective immune response is directed by Th2 lymphocytes, mirroring that observed in immunocompetent controls. Unexpectedly, abbreviation of primary infections of unreconstituted SCID mice with the drug ivermectin induces resistance to reinfection with microfilariae at a level equivalent to that induced in secondarily infected, immunocompetent controls. In contrast to protection mediated by adoptive reconstitution, resistance induced by ivermectin-abbreviated infection occurs in the absence of T cells and in association with negligible levels of serum interleukin-5 and gamma interferon. This points to the activation of some alternative host defense mechanism that operates after the clearance of therapeutic levels of drug. Such a response could have important implications for the treatment of human onchocerciasis and may go some way in explaining the long-term suppression of microfilariae observed in patients after treatment with ivermectin.

Animals↗

PubMed1997

Early somatosensory evoked potentials in preterm infants: their prognostic utility.

We hypothesized that somatosensory evoked potentials (SEPs) recorded early in the course of a preterm infant life would be predictive of long-term neurodevelopmental outcome. We recorded unilateral, median nerve SEPs in 88 preterm infants twice in the first 3 weeks of life (SEP1 and SEP2). We found both SEP1 and SEP2 to be significantly associated with the presence of periventricular leukomalacia on head ultrasound (p = 0.04 and p = 0.02 for SEP1 and SEP2, respectively). Both SEP1 and SEP2 were predictive of later cerebral palsy (CP) (p = 0.03 and p = 0.003, respectively). False-positive results were frequent (13 of 17 for SEP1 and 20 of 28 for SEP2). A normal SEP, even when there was periventricular echogenicity on head ultrasound, was associated with a normal outcome in all but 1 instance. SEP1 and SEP2 were less accurate than head ultrasound findings of periventricular leukomalacia in the prediction of later CP (73, 69 and 93%, respectively). SEPs done in the first 3 weeks of life may provide additional prognostic information, particularly when the test is normal. Abnormal SEPs in this period must be interpreted cautiously.

Cerebral Palsy↗

PubMed1997

Visual evoked potentials for prediction of neurodevelopmental outcome in preterm infants.

Visual evoked potentials (VEPs) have proved to be accurate predictors of outcome in term infants with hypoxic-ischemic encephalopathy. Parallels between term asphyxia and hypoxic-ischemic injury in the preterm brain suggested the hypothesis that VEPs may predict the development of periventricular leukomalacia (PVL) and later cerebral palsy. 123 infants less than 32 weeks' gestational age were enrolled in the study. VEPs were done in the first 3 weeks of life (usually first week). VEPs did show a statistically significant association with PVL (p < 0.04) although false-positive recordings were twice as frequent as true-positive recordings. VEPs were not associated with grade III-IV intraventricular hemorrhage (p = 1.0). Unlike asphyxiated term infants, VEPs were not predictive of abnormal neurodevelopmental outcome in the preterm population.

Aging↗

PubMed1996

Synthesis and activity of a novel series of 3-biarylquinuclidine squalene synthase inhibitors.

Quinuclidines with a 3-biaryl substituent are a new class of potent, orally active squalene synthase (SQS) inhibitors. Variants around these rigid structures indicate key structural requirements for cationic SQS inhibitors. Thus the lower in vitro potency found for quinuclidines bearing 3-substituents, which did not overlay the biphenyl group of 3-(biphenyl-4-yl)-3-hydroxyquinuclidine (2) (IC50 = 16 nM, rat microsomal SQS), implied a directional requirement for the 3-substituent. Similarly, the lower potency of the 3-terphenyl analogue 6 (IC50 = 370 nM) indicated size constraints for this substituent. In compounds with a linking group between the quinuclidine and biphenyl ring, linking groups of lower lipophilicity were less well tolerated (e.g., 17, CH2CH2, IC50 = 5 nM vs 19, NHCO, IC50 = 1.2 microM). Replacement of the distal phenyl ring of 2 with a more polar pyridine heterocycle caused a reduction in in vitro potency. In general, good in vivo activity in the rat was restricted to 3-hydroxy analogues, with the 3-[4-(pyrid-4-yl)phenyl] derivative 39 (IC50 = 161 nM) showing the best inhibition (following oral dosing) of cholesterol biosynthesis from mevalonate (ED50 = 2.7 mg/kg).

Animals↗

PubMed1996

An experimental study of the mechanical response of frozen biological tissues at cryogenic temperatures.

An experimental study of the mechanical response of frozen soft biological tissues to applied compressive stresses is presented. This study is related to the mechanical stresses that develop due to the contraction of frozen tissues in cryopreservation as well as in cryosurgical procedures. The main concept in this study is that the stresses associated with the constrained contraction of the frozen tissue, i.e., due to temperature variations within the frozen tissue, can be simulated by an external mechanical load which is applied to the frozen tissue while the tissue is maintained at a uniform temperature. A new apparatus for measuring compressive stresses and strains of frozen biological tissues in cryogenic temperature range is presented. A new technique for processing the fresh biological tissue into a cylindrical frozen sample for mechanical testing is introduced. Results of compression tests on rabbit liver, kidney, and brain are presented and are compared with available data from the literature on sea ice and single ice crystals. An unusual response of frozen biological tissues to compressive stress was observed: after the initial, roughly linear elastic portion there was a series of sudden stress drops at constant strain, each followed by a linear increase of stress with strain to the next drop. This phenomenon, which is attributed to the accumulation of microcracks, broadly resembles plastic deformation, and thus provides some support for simple mechanical models invoked in theoretical studies.

Animals↗

PubMed1996

Susceptibility of Brugia malayi and Onchocerca lienalis microfilariae to nitric oxide and hydrogen peroxide in cell-free culture and from IFN gamma-activated macrophages.

The susceptibility of Brugia malayi and Onchocerca lienalis microfilariae to H2O2 and NO either in cell-free culture or from IFN gamma-activated macrophages was examined. In cell-free culture, O. lienalis microfilariae were highly susceptible to H2O2 induced toxicity, exhibiting rapid reductions in motility and viability. The addition of exogenous catalase abrogated H2O2-induced killing. In contrast, B. malayi microfilariae were relatively resistant to H2O2, with concentrations as high as 50 microM having no effect on motility or viability. On exposure to NO, both species showed reductions in motility within 5-30 min, but longer was required to see effects on the viability of microfilariae. Parasites incubated with IFN gamma-activated macrophages also exhibited marked reductions in motility and viability. In cultures with B. malayi and activated macrophages, inhibition of these effects was achieved by the addition of either L-NMMA, to abolish NO production, or neutralizing anti-TNF alpha antibodies. Attempts to inhibit parasite killing by the addition of catalase to macrophage cultures were ineffective. The results of this study show that B. malayi and O. lienalis microfilariae have different susceptibility to H2O2, but are equally affected by exposure to NO. Moreover both species are killed by IFN gamma-activated macrophages and in the case of B. malayi, killing is dependent on the generation of NO via TNF alpha.

Animals↗

PubMed1996

Eosinophils are the major effector cells of immunity to microfilariae in a mouse model of onchocerciasis.

Mice inoculated with microfilariae of the filarial nematode Onchocerca lienalis clear their parasites over a period of 3-4 months and are highly resistant to re-infection. We have investigated the comparative roles of the eosinophil, macrophage and neutrophil in effecting this parasite clearance, employing agents specifically to perturb cell function in vivo. Using the anti-IL-5 monoclonal antibody TRFK-5, we show that eosinophils are of primary importance in effecting resistance to re-infection. Ablation of macrophages (with carbon) and neutrophils (with the monoclonal antibody NIMP-R14) had no effect on parasite clearance following re-infection. Neutralization of these 3 cell types during a primary infection showed that while the removal of both eosinophils and macrophages caused a small but significant delay in parasite clearance, the depletion of neutrophils had no effect. This report describes the first direct evidence for eosinophil-mediated killing of microfilariae in vivo, and is consistent with Th-2 cell responses previously described in this model.

Animals↗

PubMed1996

Characterization of a secreted antigen of Onchocerca volvulus with host-protective potential.

A cDNA designated MOv2 was isolated from an Onchocerca volvulus library on the basis of its product's recognition by an antiserum raised against the infective stage. Immunogold electron microscopy revealed a high density of antigenic sites associated with the annulae of the L3 cuticle and with the uterine wall of the adult female: a general, low density of labelling occurred in all developmental forms. Western blotting confirmed the presence of the antigen throughout the life cycle and the existence of an immunologically cross-reactive homologue in the related filaria, Acanthocheilonema viteae. The antigen was shown to be secreted by infective larvae and adult females of A. viteae. Sequence comparisons revealed two homologues of MOv2 (Ov-20, Ov-9) which had been selected independently by other laboratories on the basis of their specific recognition by human onchocerciasis infection sera. The IgG antibody response against MOv2 in cattle experimentally infected with O. lienalis revealed the induction of a response during the prepatent period that was strongly boosted at the onset of patency. However, only a proportion of infected cattle responded with a detectable level of anti-MOv2 antibodies. The appearance of MOv2 in larval cuticle and secretions prompted us to evaluate it as a candidate molecule for prophylactic immunization. Trials performed in the A. viteae/Mongolian jird model of filariasis revealed that recombinant MOv2 induced a host-protective response, reducing worm recoveries by 36-55% following a challenge infection.

Amino Acid Sequence↗