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Biomedical subjects

J L Taylor

Publications and source records attributed to J L Taylor.

At least 73 records · Page 4Linked to original sources
PubMed1998

A novel bioassay for the determination of neutralizing antibodies to IFN-beta1b.

We have adapted the new MxA gene-induction bioassay to measure neutralizing antibodies to interferon-beta1b (IFN-beta1b, the active ingredient in Betaseron) in sera from patients treated with Betaseron. This antibody assay has been validated to quantify neutralizing titers of 1:20 and above, with a precision of +/- 0.20 in log10. We have used this MxA gene-induction antibody assay to reinvestigate serum samples from multiple sclerosis (MS) patients treated with Betaseron. The titers measured were closely comparable to those obtained in antiviral assays. Data obtained by both methods show that neutralizing antibodies may appear and subsequently disappear over time in the sera of some patients treated with Betaseron. Sera from some patients contain binding antibodies to IFN-beta1b. It was shown that binding antibody titers do not correlate quantitatively or qualitatively with neutralizing antibody titers, and indeed, a number of patients develop high levels of binding antibodies but never form measurable levels of neutralizing antibodies.

Antigen-Antibody Reactions↗
PubMed1998

The comparative anti-herpes simplex virus effects of human interferons.

The mechanism(s) of anti-herpes simplex virus (HSV) activity of interferons (IFNs) have not been clearly identified. We have tested natural and recombinant human IFN-alpha, IFN-beta, and IFN-gamma preparations for their relative anti-HSV activity in human corneal and Vero monkey kidney cells. The relative anti-HSV activities in corneal cells were IFN-beta > rIFN-gamma > IFN-alpha (lymphoblastoid) > rIFN-beta2a = rIFN-alphaA/D. IFN-beta at 100 IU/ml reduced virus yield by 59+/-24%. The relative anti-HSV activity in Vero cells was rIFN-gamma > IFN-beta = IFN-alpha (lymphoblastoid) > rIFN-alphaA/D > rIFN-alpha2a. IFN-gamma at 100 IU/ml reduced virus yields by 90+/-4%. Reducing the multiplicity of infection significantly increased the apparent antiviral activity of all IFNs. The antiviral activity of IFNs could be detected by 4 h after treatment of Vero cells but not until 8 h in corneal cells. Western blot analysis showed that none of the IFNs detectably reduced the levels of immediate-early HSV protein, ICP4, but some reduced ICP0 levels early during infection, the extent and duration of the reduction varying with both IFN and cell type. The greatest effects on viral protein levels were detected in IFN-y-treated Vero cells. These data indicated that the targets of the anti-HSV activities of IFNs can vary with both IFN and cell type.

Animals↗
PubMed1998

Everyday problem solving among individuals with Alzheimer's disease.

Loss of functioning on complex tasks of daily living is an early indicator of dementia. The performance of 65 older adults with mild to moderate levels of Alzheimer's disease was examined on the Everyday Problems Test for the Cognitively Challenged Elderly (EPCCE), self-report inventories of functional performance, and a broad battery of clinical and neuropsychological measures. The EPCCE was designed to assess older adults on a set of complex tasks of daily living that involved not only global cognitive processes, but also higher-order executive functions. Participants solved an average of 45% of EPCCE tasks with significant differences in scores by disease severity. Performance was significantly related to global cognitive functioning and disease severity, and in particular to executive functions. Significant additional variance was accounted for by these executive functions beyond the variance accounted for by global cognitive measures.

Activities of Daily Living↗
PubMed1998

Lung-specific induction of heme oxygenase-1 and hyperoxic lung injury.

Heme oxygenase (HO)-1, which catalyzes heme breakdown, is induced by oxidative stress and may protect against oxidative injury. We hypothesized that induction of HO-1 by hemoglobin (Hb) in the lung would protect the rat from pulmonary O2 toxicity. Rats given intratracheal (i.t.) Hb showed lung-specific induction of HO-1 by 8 h by Western analysis. Rats were then pretreated for 8 h before 60 h of exposure to 100% O2 with either IT normal saline, HB, or Hb plus the HO-1 inhibitor tinprotoporphyrin (SnPP). Both the Hb + O2 and Hb + O2 + SnPP animals had less lung injury than normal saline controls as indicated by lower pleural fluid volumes and wet-to-dry weight ratios (P < 0.01). The improvement in injury in the two Hb-treated groups was the same despite a 61% decrease in HO enzyme activity in the Hb + SnPP group after 60 h of O2. In addition, inhibition of HO activity with SnPP alone before O2 exposure did not augment the extent of hyperoxic lung injury. These results demonstrate that IT Hb induces lung HO-1 in the rat and protects against hyperoxia; however, the protection is not mediated by increased HO enzyme activity.

Animals↗
PubMed1998

Induction of ferritin and heme oxygenase-1 by endotoxin in the lung.

Heme oxygenase (HO)-1 expression is increased by forms of oxidative stress that also induce ferritin. Even though this could result from release of iron by heme degradation, we hypothesized that ferritin expression in the lung after endotoxin [lipopolysaccharide (LPS)] would occur independently of HO-1 because iron sequestration is an important response to infection. We tested this hypothesis by instilling saline or LPS (1 mg) into lungs of rats and measuring ferritin expression, HO-1 expression and activity, and HO-1 and ferritin mRNAs at different times. Lungs were also inflation fixed for immunohistochemistry for HO-1 and ferritin. Studies were performed with and without the HO inhibitor tin protoporphyrin. Ferritin and HO-1 labeling were minimal (macrophages only) in control lungs. By 4 h after LPS instillation, ferritin staining was present in bronchial epithelium and macrophages, became diffuse at 16 h, and was nearly gone by 48-72 h. HO-1 was detectable in macrophages 4 and 16 h after LPS instillation, increased in macrophages and bronchial epithelium at 24 h, and diffusely increased in bronchial epithelium and the alveolar region at 48-72 h. Lung ferritin content increased significantly by 4 h and peaked at 16 h before declining. HO-1 protein was present by Western blot in control lung, stable at 4 h, and increased by 24 h after LPS instillation, whereas HO enzyme activity had increased by 4 h after LPS instillation. After complete inhibition of HO enzyme activity with tin protoporphyrin, ferritin increased threefold at 4 h and sixfold at 24 h after LPS instillation. HO-1 mRNA increased by 4 h and was sustained at 24 h, whereas ferritin mRNA did not change after LPS instillation. These results indicate that intratracheal LPS rapidly induces ferritin protein in the lung independently of its mRNA synthesis or HO enzyme activity. LPS induces HO-1 mRNA, which is followed by increased expression of protein.

Animals↗
PubMed1998

The effects of interferon-alpha on the production and action of other cytokines.

Various interferon-alpha (IFN-alpha) preparations, either as individual subtypes or natural mixtures, induce or inhibit expression of several other cytokines, as well as cytokine receptors and chemokines. The cytokines and receptors reportedly affected by IFN-alpha include interleukin-1 (IL-1), IL-2, IL-6, IL-8, IL-1 receptor, IL-1 receptor antagonist, tumor necrosis factor, tumor necrosis factor receptor, and IFN-gamma, all of which may amplify the effects of IFN-alpha treatment. The mechanism by which IFN-alpha induces expression of these cytokines is not clear. Some of the therapeutic and toxic effects associated with IFN-alpha therapy may be caused by the induction or inhibition of other cytokines and their respective cellular effects. Side effects including fever, anorexia, and fatigue can be caused by one or more of the cytokines induced by IFN-alpha. The response of different cell types, normal or malignant, to cytokines can vary. Such variation in cell type-specific responses may contribute to the diverse array of physiologic effects associated with IFN-alpha therapy. Further research is required to systematically uncover how other cytokines, receptors, or cellular factors contribute to the therapeutic and toxic effects of IFN-alpha.

Cytokines↗
PubMed1998

Toxic-Pfiesteria--surveillance for human disease in Maryland.

The presence of toxic stages of the dinoflagellate Pfiesteria piscicida and other morphologically related organisms was documented in three estuarine waterways on the lower Eastern Shore of Maryland in 1997. The Maryland Department of Health and Mental Hygiene, working closely with the local health departments, established a surveillance system to collect reports of human illnesses. Maryland's experience has formed the base on which national surveillance criteria for Estuary Associated Syndrome have been developed and regional surveillance protocols have been built. The cooperation of practicing physicians is essential to continued surveillance efforts to further delineate the extent and nature of human health effects following exposures to waters where toxic forms of these dinoflagellates are active. Physicians wishing to report persons who may have Estuary Associated Syndrome should contact their local health department. Persons wanting information or wishing to report finding lesioned fish or a fish kill in progress should call the Maryland Pfiesteria Hotline at 1- 888-584-3110.

Animals↗
PubMed1998

Tissue-specific accumulation of latency-associated transcripts in herpes virus-infected rabbits.

PURPOSE: Herpes simplex virus (HSV) DNA persists in the corneas of patients and animals with a history of herpetic keratitis. The purpose of this study was to detect viral transcripts in the corneas of latently infected rabbits with a history of herpetic keratitis to determine whether the viral DNA represents latent virus, characterized by the restricted transcription of HSV genes and accumulation of the stable latency-associated transcripts (LATs), as occurs in neurons. METHODS: Rabbits were injected in the subalveolar mucosa with HSV strain RE. After 30 days, corneas were infected by intrastromal injection of HSV. Corneal disease was evaluated, and 7 to 378 days after infection, the rabbits were killed. DNA and RNA were isolated from corneas and trigeminal ganglia and amplified by PCR using gene-specific primers. RESULTS: Herpetic keratitis developed in all rabbits. All corneas of these immune rabbits contained viral DNA as many as 120 days after infection and then the frequency decreased over the next 260 days. Overall, viral DNA was detected in all ganglia and in 57% of corneas. All latently infected ganglia but no corneas contained LATs. Transcripts of the early viral gene for thymidine kinase were detected in 23 of 30 ganglia and 10 of 17 corneas. Transcripts for the late viral glycoprotein C were not detected in either tissue. CONCLUSIONS: These data document that after HSV keratitis, viral DNA persists in corneas in the absence of stable LATs and with restricted expression of other viral genes.

Animals↗
PubMed1997

Pharmacoeconomic comparison of treatments for the eradication of Helicobacter pylori.

BACKGROUND: Patients with Helicobacter pylori-induced duodenal ulcer should have their infection eradicated. The optimal choice of antibiotic therapy, however, is less clear. OBJECTIVE: To evaluate costs and outcomes of treatment with 8 antibiotic regimens with documented activity against H pylori vs maintenance therapy with histamine2-receptor antagonists (H2RA). METHODS: A meta-analysis for 119 studies enrolling 6416 patients to determine aggregate eradication rates. The complexity of each regimen was used to determine the anticipated compliance rate and actual effectiveness. A decision analytic model with Monte Carlo simulation determined annual costs and health outcomes. RESULTS: Average annual total costs of testing for H pylori infection and antibiotic treatment ranged from $223 to $410 and prevented ulcer recurrence in 70% to 86% of patients. The H2RA maintenance therapy cost $425 and prevented recurrence in 72% of patients. The lowest costs and recurrence rates were achieved by 3 regimens: standard triple therapy (a combination of bismuth subsalicylate, metronidazole, and tetracycline hydrochloride) for 14 days ($223, with 18% recurrence); a combination of clarithromycin, metronidazole, and a proton pump inhibitor for 7 days ($235, with 15% recurrence); and standard triple therapy with a proton pump inhibitor for 7 days ($236, with 14% recurrence). CONCLUSION: Treatment with any regimen resulted in lower costs compared with H2RA maintenance therapy. Three antibiotic regimens had consistently lower costs and better outcomes: standard triple therapy for 14 days, metronidazole, clarithromycin, and a proton pump inhibitor for 7 days, and standard triple therapy plus a proton pump inhibitor for 7 days.

Anti-Bacterial Agents↗
PubMed1997

Effect of contraction strength on responses in biceps brachii and adductor pollicis to transcranial magnetic stimulation.

The sizes of the motor-evoked potentials (MEPs) and the durations of the silent periods after transcranial magnetic stimulation were examined in biceps brachii, brachioradialis and adductor pollicis in human subjects. Stimuli of a wide range of intensities were given during voluntary contractions producing 0-75% of maximal force (maximal voluntary contraction, MVC). In adductor pollicis, MEPs increased in size with stimulus intensity and with weak voluntary contractions (5% MVC), but did not grow larger with stronger contractions. In the elbow flexors, MEPs grew little with stimulus intensity, but increased in size with contractions of up to 50% of maximal. In contrast, the duration of the silent period showed similar changes in the three muscles. In each muscle it increased with stimulus intensity but was unaffected by changes in contraction strength. Comparison of the responses evoked in biceps brachii by focal stimulation over the contralateral motor cortex with those evoked by stimulation with a round magnetic coil over the vertex suggests an excitatory contribution from the ipsilateral cortex during strong voluntary contractions.

Arm↗
PubMed1996

Effects of arterial perfusion pressure on force production in working human hand muscles.

1. The effects of hydrostatic changes in perfusion pressure on performance of working fatigue-resistant muscle fibres in the hand were studied in six normal subjects. 2. Supramaximal stimuli were delivered in trains of 200 ms duration, at 1 train S-1, to the ulnar nerve proximal to the wrist to produce isometric contractions of adductor pollicis. The force of contraction was measured and, after a level contraction force was achieved, the arm was passively raised or lowered. 3. Lifting the hand 45 cm above the heart produced a decline in force output from the muscle within several seconds which, after 4 min, fell by 22% below the steady-state level. Lowering the hand 45 cm below heart level produced an 8% increase in force output. Greater changes in force output occur at higher workloads. 4. It is concluded that in human subjects, muscle performance is sensitive to changes in perfusion pressure that occur across the physiological range. At moderate work levels, force output of the working muscles in the hand can vary by up to 30% over the physiological range of blood pressure. This dependence of muscular force on blood perfusion is of potential importance to motor control during normal activities.

Adult↗
PubMed1996

Changes in motor cortical excitability during human muscle fatigue.

1. The excitability of the motor cortex was investigated during fatiguing con of the elbow flexors in human subjects. During sustained contractions at 30 and 1 voluntary force (MVC), the short-latency electromyographic responses (EMG) evoke brachii and brachioradialis by transcranial magnetic stimulation increased in si EMG in the elbow flexors following the evoked muscle potential (silent period), duration during a sustained MVC but not during 30% MVCs nor during a sustained M muscle (adductor pollicis). 2. When the blood supply to brachioradialis was blocked with sphygmomanometer cuff sustained MVC, the changes in EMG responses to transcranial stimulation rapidly control values, This suggests that changes in these responses during fatigue wer small-diameter muscle afferents. 3. Tendon vibration during sustained MVCs indicated that the changes in the resp cortial stimulation were not mediated by reduced muscle spindle inputs. 4. Muscle action potentials evoked in brachioradialis by electrical stimulation cervicomedullary junction did not increase in size during sustained MVCs. Thus, cortically evoked responses during sustained MVCs reflects a change in cortical Although the silent period following cervicomedullary stimulation lengthened, it substantially shorter than the cortically evoked silent period. 5. The altered EMG responses to transcranial stimulation during fatigue suggest exitation and increased inhibition in the motor cortex. As these changes were un manipulation of afferent input they presumably result from intrinsic cortical pr altered voluntary drive to the motor cortex.

Action Potentials↗
PubMed1996

Supraspinal factors in human muscle fatigue: evidence for suboptimal output from the motor cortex.

1. Voluntary activation of elbow flexor muscles can be optimal during brief maximal voluntary contractions (MVCs), although central fatigue, a progressive decline in the ability to drive the muscle maximally, develops during sustained or repeated efforts. We stimulated the motor cortex and motor point in human subjects to investigate motor output during fatigue. 2. The increment in force (relative to the voluntary force) produced by stimulation of the motor point of biceps brachii increased during sustained isometric MVCs of the elbow flexors. Motoneuronal output became suboptimal during the contraction, i.e. central fatigue developed and accounted for a small but significant loss of maximal voluntary force. During 3 min MVCs, voluntary activation of biceps fell to an average of 90.7% from an average of > 99%. 3. The increment in force (relative to the voluntary force) produced by magnetic cortical stimulation was initially small (1.0%) but also increased during sustained MVCs to 9.8% (with a 2 min MVC). Thus, cortical output was not optimal at the time of stimulation nor were sites distal to the motor cortex already acting maximally. 4. A sphygmomanometer cuff around the upper arm blocked blood supply to brachioradialis near the end of a sustained MVC and throughout subsequent brief MVCs. Neither maximal voluntary force nor voluntary activation recovered during ischaemia after the sustained MVC. However, fatigue-induced changes in EMG responses to magnetic cortical stimulation recovered rapidly despite maintained ischaemia. 5. In conclusion, during sustained MVCs, voluntary activation becomes less than optimal so that force can be increased by stimulation of the motor cortex or the motor nerve. Complex changes in excitability of the motor cortex also occur with fatigue, but can be dissociated from the impairment of voluntary activation. We argue that inadequate neural drive effectively 'upstream' of the motor cortex must be one site involved in the genesis of central fatigue.

Adult↗
PubMed1996

Selection of motor responses on the basis of unperceived stimuli.

In a previous study, the sensory phenomenon of "backward masking" was used to demonstrate that subjects can preprogram a single stereotyped voluntary movement or movement-sequence and that such a movement can be triggered in response to a stimulus that is not perceived (that is, a stimulus of which the subject is unaware). In the present study, visual stimuli were presented at random in one of two different locations to normal human subjects in a choice reaction-time (RT) task. When the stimulus appeared in one of the locations, subjects made a motor response. When the stimulus appeared in the other location, subjects made a different motor response. Large and small stimuli were presented in either location. In some trials, the small stimulus was followed 50 ms later by the large stimulus. The small stimulus was then "masked" by the large stimulus and could not be perceived on forced-choice testing. Despite not perceiving the test stimulus in either of its randomly selected locations, subjects were able to select and execute the motor response appropriate for each location. The RTs for responses to the masked stimulus and to the same stimulus presented without masking (and so, easily perceived) were the same. This result implies that appropriate programs for two separate movements can be simultaneously held ready for use, and that either one can be executed when triggered by specific stimuli without subjective awareness of such stimuli and so without further voluntary elaboration in response to such awareness.

Analysis of Variance↗
PubMed1996

Production of ISG-15, an interferon-inducible protein, in human corneal cells.

ISG-15, a 15-kDa protein encoded by an interferon (IFN)-stimulated gene (ISG), was produced in human corneal cell cultures prepared from donor corneas in response to each of three major types of IFN, IFN-alpha, IFN-beta, and IFN-gamma. IFN-alpha and IFN-beta induced more ISG-15 in the first 24 h of treatment than did IFN-gamma. ISG-15 was detectable within the first 3 h of treatment with either type I IFN, and production peaked at 24 h, whereas IFN-gamma did not induce detectable ISG-15 until 16 h and did not induce peak production until 48 h. Conjugates of ISG-15 to cellular proteins were detectable by Western blot beginning at 9 h after IFN-alpha or IFN-beta treatment. ISG-15 persisted in IFN-treated cells for as long as 96 h. Free, unconjugated, ISG-15 was secreted by keratocytes into cell culture medium. The extent and kinetics of production, the conjugation of ISG-15 to cell proteins, and the secretion of ISG-15 in human fibroblast derived from corneas were IFN type dependent and dose dependent.

Cells, Cultured↗
PubMed1996

Herpetic stromal disease: response to acyclovir/steroid therapy.

The efficacy of combined acyclovir and steroid therapy in the treatment of herpetic stromal disease was evaluated by clinical evaluation of disease, the rebound of disease following termination of therapy, and the recovery of virus and viral DNA from corneas in a rabbit model. Therapy with acyclovir alone produced a significant reduction in corneal thickness in 10% of eyes. Addition of steroid to acyclovir therapy decreased the severity of stromal disease as measured by corneal thickness and increased the frequency of response to treatment to 63% of eyes. All eyes receiving acyclovir alone experienced rebound of disease following termination of therapy. Combined therapy increased the severity of rebound of corneal disease. Virus was recovered from cell cultures established after recovery from rebound in 50% of untreated and treated eyes. Viral DNA was detected by PCR in five of the nine corneal cultures which did not produce infectious virus.

Acyclovir↗
PubMed1996

Assessment of antiviral activity, efficacy, and toxicity of prostaglandin A2 in a rabbit model of herpetic keratitis.

Prostaglandin A2 (PGA2) inhibited the replication of herpes simplex virus type 1 in rabbit and human cornea stromal cells at concentrations of 1 to 5 microM while causing significant toxicity at 55 to 150 microM. Despite favorable therapeutic indices in cultured cells, PGA2 was not effective as a therapeutic agent in the treatment of herpetic keratitis in a rabbit model. The sequelae of disease appeared more severe in animals receiving PGA2 than in untreated or placebo-treated controls. The recovery of virus from tissues of latently infected rabbits was not affected by therapy. PGA2 therapy alone induced breakdown of the blood-aqueous barrier, indicating that pharmacologically active concentrations of drug were achieved in the eye. Thus, PGA2 had antiviral activity, but its proinflammatory effects appeared to be more detrimental than beneficial in the treatment of herpetic keratitis.

Animals↗