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Biomedical subjects

J L Taylor

Publications and source records attributed to J L Taylor.

At least 127 records · Page 7Linked to original sources

Illusions of head and visual target displacement induced by vibration of neck muscles.

Vibration of the posterior muscles of the neck in human subjects induces illusions of displacement and movement of a visual target when there is no visual reference (Biguer et al., 1988). Although illusions of head movement are rarely reported by subjects, when they point to the location of the nose they demonstrate an alteration of the perceived position of the head. The kinaesthetic illusion is in a direction consistent with the visual illusion but is of smaller magnitude.

Head↗

Endogenously produced interferon alpha protects mice from herpes simplex virus type 1 corneal disease.

Intravenous (i.v.) injection of u.v. light-inactivated herpes simplex virus type 1 (UV HSV-1) at the time of HSV-1 corneal infection reduced the cytotoxic T lymphocyte (CTL) response to HSV-1, and significantly reduced the incidence of HSV-1-induced corneal stromal disease in A/J mice. The spread of HSV-1 through the eye after corneal infection, detected using engineered HSV-1 (US3::Tn5-lacZ) with the lacZ gene under the transcriptional control of the viral late gene promoter for glycoprotein C, was also markedly reduced by i.v. UV HSV-1 injection. The restriction of HSV-1 corneal invasiveness in i.v. UV HSV-1-injected mice preceded the onset of a detectable specific cell-mediated or humoral immune response to HSV-1, and was accompanied by an elevated serum titre of interferon (IFN-alpha), reversed by anti-IFN-alpha/beta antibody, and mimicked by systemic IFN-alpha treatment. IFN-alpha-treated mice developed a normal CTL response to HSV-1 after corneal infection, but the corneal invasiveness of the virus was markedly reduced and none of the treated mice developed corneal stromal disease. Together with our previous findings that HSV-1-specific CTLs participate in the pathogenesis of corneal stromal disease, these results indicate that i.v. injection of UV HSV-1 at the time of corneal infection may prevent stromal disease by the combined effects of IFN-mediated reduction of the spread of virus in the cornea and inhibition of the activity of the HSV-specific T lymphocytes that induce tissue destruction in the corneal stroma.

Animals↗

The development of corneal edema in herpes simplex virus type 1-infected rabbits following termination of therapy for corneal stromal disease.

One complication of combined antiviral/corticosteroid therapy for herpetic stromal disease in patients is rebound of disease upon termination of therapy. To develop a model of steroid rebound, rabbits were injected intrastromally with 10(3) pfu of HSV-1 (RE strain). Therapy with 1% trifluorothymidine (F3TdR) alone or in combination with immunosuppressive agents was initiated 7 days post-infection, at a time when epithelial disease had reached its peak and corneal thickness had begun to increase. Therapy was continued 5 times daily through day 18 post-infection. Following cessation of therapy 13 of 16 eyes receiving both 1% F3TdR and 0.125% prednisolone acetate experienced rebound of disease characterized by an increase in corneal thickness from 514 +/- 106 microns to 743 +/- 189 microns, reaching a maximum at 27 +/- 3 days post-infection. Rabbits receiving therapy with either phosphate buffered saline or F3TdR alone displayed rebound in 2 and 3 of 12 eyes, respectively. Rabbits receiving F3TdR combined with either cyclosporine or deoxycoformycin experienced rebound of disease in 9 of 20 and 6 of 16 eyes, respectively. Cultures of eye washings taken from eyes at the time of rebound were negative in all cases. The data indicate that only steroids significantly increased the proportion of eyes with rebounding stromal disease and corneal edema. These studies document steroid rebound of stromal disease in an animal model.

Animals↗

Combined anti-herpes virus activity of nucleoside analogs and interferon.

Addition of interferon (IFN) to nucleoside analog therapy for herpetic keratitis has been shown to significantly increase the efficacy of therapy compared to nucleoside alone. We have analysed several nucleoside analogs and recombinant IFN-alpha 2 to determine which combinations have increased anti-herpes simplex virus type 1 (HSV) activity. Synergistic anti-HSV activity between IFN-alpha 2 and the acyclic guanosine analogs, acyclovir (ACV) and ganciclovir (DHPG), was demonstrated in cytopathic effect reduction assay in human corneal cell cultures as well as in Vero cells. In this assay system IFN-alpha 2 alone had little detectable antiviral activity at titers of greater than or equal to 2,000 IU/ml, however, treatment of cells with about 100 IU/ml of IFN-alpha 2 for 24 hrs prior to infection decreased the ED50 of ACV approximately 2- to 3-fold and of DHPG approximately 5- to 6-fold in Vero cells. Combinations of IFN-alpha 2 with bromovinyldeoxyuridine (BVdU) in Vero cells or human corneal stromal cells did not increase the antiviral activity of BVdU. Combinations of IFN-alpha 2 with trifluorothymidine (TFT) also did not increase the effective antiviral activity of this nucleoside and resulted in decreased uptake of TFT from the medium. These studies document that combinations of acyclic nucleoside analogs, ACV and DHPG, with IFN-alpha 2 resulted in synergistic anti-HSV activities in both Vero and human corneal stromal cells, while the pyrimidine analogs, TFT and BVdU, were not synergistic with IFN-alpha 2. IFN-alpha 2 treatment of cells induced modifications of nucleoside (e.g., thymidine and TFT), but not nucleobase (e.g., ACV) uptake. These studies suggest that selective inhibition of nucleoside versus nucleobase uptake may contribute to the mechanism of IFN/nucleobase synergy in the inhibition of HSV replication.

Animals↗

Therapeutic response of herpes simplex virus-induced corneal edema to trifluridine in combination with immunosuppressive agents.

Herpetic stromal disease often is treated with combinations of antiviral agents and corticosteroids. The addition of steroids to the antiviral treatment regimen frequently increases the efficacy of therapy in patients; however, many complications may arise as a result of corticosteroid therapy. Using a rabbit model, the effects of trifluridine (F3TdR) on corneal edema and stromal disease were examined when combined with each of three immunosuppressive agents. The therapeutic response was evaluated by classifying eyes as either responsive or unresponsive based on the maximum corneal thickness attained during therapy. The data indicate that about 56% of the eyes responded to therapy with 1% F3TdR alone even when therapy was initiated after signs of stromal inflammation had begun to appear and epithelial disease was resolving. Combination of F3TdR with 0.125% prednisolone acetate significantly increased the proportion of responsive eyes to about 78%. Therapy with F3TdR combined with topical 5% cyclosporine A was no better than F3TdR alone, and combination with 0.2% deoxycoformycin and 0.4% 2'-deoxyadenosine significantly decreased the proportion of responsive eyes. These data further document that the responses of stromal disease to therapy must be evaluated on an eye-by-eye basis because the distribution of the data may not be Gaussian in nature. Eyes with corneal edema and stromal disease induced by herpes simplex viral (HSV) infection may respond to therapy with antiviral agents alone, but others require steroid. Still others do not respond to combined therapy. Combining the responses of all eyes in a given treatment group to obtain a "population mean" may be misleading.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Proprioceptive sensation in rotation of the trunk.

Proprioceptive sensation in rotation of the trunk about a vertical axis was investigated in normal human subjects. Subjects pointed at the big toe with the nose to test the accuracy of positioning of the trunk. Active rotation of the head and shoulders on the stationary hips and legs to align the nose and toe, was not significantly more accurate than moving the hips, legs and toe under the fixed head and shoulders. Passive displacements were imposed on the head and shoulders, or on the hips and legs. Thresholds for the detection of these displacements were unchanged by the exclusion of vestibular stimulation. Thresholds were highest (still less than 1 degree) at the slowest angular velocity (0.1 degree/s) and became lower as the angular velocity was increased.

Adult↗

Vascular anomalies of the scalp.

Paediatricians and surgeons of different disciplines are referred vascular anomalies of the scalp from time to time. These rare lesions may produce serious side-effects and the authors review the treatment of these abnormalities illustrated by five cases. Where possible, total excision is the treatment of choice.

Adolescent↗

Recent progress in interferon research: molecular mechanisms of regulation, action, and virus circumvention.

A complex system of cis regulatory elements exists by which induction of IFN gene expression is initiated in response to a variety of inducers; cis elements also appear to be involved in the down-regulation of IFN production. IFN gene activation or inhibition of expression may be tightly regulated by the specific binding of newly synthesized or modified proteins to be regulatory regions of the IFN genes. IFN itself acts as a potent modulator of multiple cellular activities. By binding to specific cell surface receptors and probable internalization via receptor-mediated endocytosis and transport into the dense chromatin, IFN treatment leads to activation of numerous genes, some of which possess known antiviral or immunoregulatory functions, whereas the function of others remains to be identified. As with the IFN genes themselves, many of the IFN-inducible genes appear to possess complex regulatory mechanisms, including domains for binding of specific trans-acting proteins. To add to this molecular complexity some viruses have successfully developed methods to circumvent, among other mechanisms, the 2',5'-A-mediated system and the P1 protein kinase system.

Animals↗

Ability to detect angular displacements of the fingers made at an imperceptibly slow speed.

The ability to detect very slow rotations, which were associated with no sense of movement, was tested at the metacarpophalangeal (MCP), proximal interphalangeal (PIP) and distal interphalangeal (DIP) joints of the middle finger of human subjects. This ability was termed 'position sense'. All the joints were found to have a position sense. No difference in detections of different angular displacements was demonstrated between the joints. Contraction, after the completion of a displacement, of the muscles operating the joints did not alter the position sense. In addition, the DIP joint was also examined in a posture that functionally disengaged its flexor and extensor and no change in position sense was found.

Finger Joint↗

Task-dependent changes in gain of the reflex response to imperceptible perturbations of joint position in man.

1. It has been demonstrated recently that, when suitably instructed, subjects could alter the stiffness at the elbow in response to a slowly and imperceptibly changing elastic load. Although evidence was provided in favour of this occurring via changes in gain of the reflex response to stretch, changes in the degree of co-contraction could not be entirely ruled out. The major objective of the present experiments was to determine if subjects could alter stiffness at the wrist in a similar task, and then to determine whether they retained this ability when co-contraction was made impossible by anaesthetizing the nerve to the wrist extensors. A second objective was to determine if changes in stiffness could be controlled independently at the wrist and elbow. 2. Subjects, with eyes closed, initially held position constant against a constant force that loaded the flexors. For the wrist, they were instructed: (i) to keep the hand as still as possible (keep position constant) or (ii) to let the hand be moved by the perturbation (keep force constant). The perturbation was an initially imperceptible elastic load whose direction (loading or unloading) could not be predicted. Subjects were also asked to indicate when the perturbation was first perceived. 3. When asked to hold position constant or force constant at the wrist, subjects demonstrated task-dependent changes in stiffness prior to perception of the perturbation. These changes in stiffness were still achieved when the nerve to the wrist extensors was anesthetized and thus co-contraction was prevented. 4. Five subjects demonstrated the ability to control stiffness independently at the wrist and the elbow although most subjects had difficulty with the task we employed to demonstrate this. 5. The results demonstrate: (i) that for the wrist, set-dependent changes in stiffness that occur prior to perception of a slowly developing perturbation can be mediated by changes in gain of reflex responses to those perturbations, and (ii) that stiffness can be controlled independently at the wrist and elbow, presumably in part by changes in gain of stretch reflexes.

Elbow Joint↗

Nucleoside metabolism in herpes simplex virus-infected cells following treatment with interferon and acyclovir, a possible mechanism of synergistic antiviral activity.

Alpha interferon (IFN-alpha) and nucleoside analogs have been shown to have synergistic antiherpesvirus activity in cultured cells. The mechanisms responsible for this synergistic activity are not known, but we hypothesize that IFN-alpha-induced alterations of nucleoside metabolism in virus-infected cells may play an important role. Infection of cells with herpes simplex virus type 1 (HSV-1) led to an increase in uptake of thymidine into cells. Treatment of infected cells with recombinant IFN-alpha for 24 h prior to infection resulted in a significant reduction in the uptake of exogenous thymidine but did not reduce the apparent incorporation of exogenous thymidine into DNA. The amount of exogenous thymidine phosphorylated relative to the amount taken up was the same in IFN-alpha-treated and control cultures. IFN-alpha treatment of HSV-1-infected cells also resulted in a reduction in the pool sizes of endogenous deoxyribonucleoside-5'-triphosphates relative to those of untreated HSV-1-infected cultures. Although IFN-alpha affected the metabolism of natural nucleosides in HSV-1-infected cells, it did not significantly reduce the uptake of the antiviral guanosine analog acyclovir into HSV-1-infected cells or the amount of acyclovir-5'-triphosphate accumulated. Therefore, in IFN-alpha-treated cells the concentration of a natural nucleoside, thymidine, was reduced, as were the pools of all deoxyribonucleoside-5'-triphosphates. No decrease in acyclovir or acyclovir-5'-triphosphate concentration was observed, however, when acyclovir-treated cells were exposed to IFN-alpha. These data suggest that IFN-alpha-induced alterations in nucleoside metabolism may be one mechanism whereby IFN-alpha and acyclovir express synergistic antiherpes-virus activity.

Acyclovir↗

Delayed rupture of the spleen in rheumatoid arthritis.

When tripping and falling patients with rheumatoid arthritis may adopt the 'fetal tuck' position to protect their painful deformed hands. There is then a risk of splenic injury by the left elbow, which may not be immediately apparent.

Accidental Falls↗

Pathogenesis of corneal oedema associated with herpetic eye disease.

Corneal oedema and stromal disease, induced in rabbits by intrastromal injection of herpes simplex virus, type 1, strain RE (HSV-1, RE), reached a peak of 12-15 days after infection. Corneal oedema as measured by ultrasonic pachymetry, and stromal disease as measured by a subjective scoring system, were closely related for 30 days after infection. Morphometric analysis of wide field specular micrographs showed that no immediate endothelial cell damage occurred in either control or HSV-1 infected corneas. Alizarin red S staining of corneas taken during the period of most severe oedema indicated no significant endothelial cell loss; however, visual inspection indicated numerous staining abnormalities. Scanning and transmission electron microscopy provided evidence of an intact endothelial layer possessing integrated infiltrating cells. Virus antigen could not be detected on endothelial cells by immunoperoxidase staining at any time during development of corneal oedema. The results indicate that corneal oedema associated with HSV-1 induced disease can occur in the absence of detectable virus replication and cytolysis of corneal endothelial cells.

Animals↗

Disintegration of mercury disc cells in simulated gastric juice: implications for management of disc cell ingestion.

The disintegration of charged alkaline mercury button cells in simulated gastric fluid over a 24 h period has been studied. The integrity of the cells and the amount of mercury that can leak out of them were assessed. The cells raised the pH of the incubating solutions. Disruption was seen in five out of 18 cells tested in 0.1 mol/L hydrochloric acid and one out of nine in 0.9% saline. Five of the six disrupted cells were made by the same manufacturer. Major leakage of mercury only occurred after complete disintegration of the cells. The implications of these findings for the management of patients who have ingested mercury-containing button cells are discussed.

Animals↗

Triggering of preprogrammed movements as reactions to masked stimuli.

1. Visual stimuli were presented to normal human subjects to test simple and more complex voluntary motor responses. Large and small visual stimuli were presented. In some trials, the small stimulus was followed 50 ms later by the large stimulus, so that the small stimulus was not perceived; this is the phenomenon of "backward masking." 2. Although subjects were not able to detect the masked, visual stimulus on forced-choice testing, they performed motor, reaction-time (RT) tasks in response to it. The RTs for responses to the masked stimulus were the same as those for responses to the easily perceived, nonmasked stimulus. 3. This result confirms and extends the findings of Fehrer and Biederman and was demonstrated with both simple and more complex motor responses. 4. Discussion of the findings focuses on their implications for motor control, particularly with respect to the preprogramming of voluntary movement.

Humans↗

Overcoming barriers to blood pressure control in the elderly.

Given the evidence that treating hypertension reduces the morbidity and mortality associated with it, and given the demonstrated effectiveness of the antihypertensive agents available, the number of inadequately controlled patients is disturbing. Failed or inadequate antihypertensive therapy may be due to aging-related pharmacokinetic and pharmacodynamic changes, drug interactions, poor patient compliance, or poor communication between physician and patient. By understanding the reasons for therapeutic failure in hypertension, the primary care physician is in a position to remedy the problem. It is the uncommon patient whose blood pressure can not be controlled if the doctor is giving proper advice which the patient then follows.

Aged↗

Interferon receptors and their role in interferon action.

Interferon (IFN) proteins interact with cells through specific cell surface receptors, some of which have been purified and cloned. The alpha-IFNs and beta-IFN bind to a common receptor (type I), whereas gamma-IFN binds to a separate receptor (type II). Both types of high-affinity receptors have been demonstrated on a variety of receptors and the ways in which IFNs may affect cellular physiology and gene expression is discussed.

Animals↗