Biomedical subjects
Publications and source records attributed to J L Taylor.
All isolates examined of the phytopathogenic fungus Leptosphaeria maculans that are aggressive to Brassica napus and Brassica rapa have a repetitive element, LMR1. Horizontal transfer of LMR1 to an isolate of a closely related species of Leptosphaeria correlates with the expansion of the host range of this isolate to include Brassica juncea.
The 2',5'-oligoadenylate (2-5A) synthetase pathway, induced by interferon-alpha (IFN-alpha), has been shown to be responsible for the antiviral action of IFN-alpha against some viruses. Studies were done to determine the role of this pathway in the anti-herpes simplex virus (HSV) action of IFN-alpha alone or in combination with acyclovir (ACV), a combination that leads to synergistic anti-HSV activity. Treatment of human corneal cells or Vero cells with 100 IU/ml of IFN-alpha induced expression of 2-5A synthetase mRNA and a 10-fold increase in 2-5A synthetase production compared with untreated cells. HSV infection alone did not induce 2-5A synthetase production, but when IFN-alpha-treated cells were infected with HSV, enzyme level was significantly increased (p < 0.05) compared with that in IFN-alpha-treated, uninfected cells. HSV infection actually decreased the level of 2-5A synthetase mRNA in IFN-alpha-treated cells. Although IFN-alpha treatment induced high levels of 2-5A synthetase with or without HSV infection, no activation of the latent endonuclease was detected by specific cleavage of ribosomal RNA. Treatment of infected cells with 5 microM ACV alone or combined with IFN-alpha did not increase 2-5A synthetase or endonuclease activities above those detected in cells not treated with ACV. The data indicate that the 2-5A synthetase pathway was inducible in corneal cells and Vero cells but did not appear to contribute to the anti-HSV activity of IFN-alpha alone or the synergistic activity of IFN-alpha combined with ACV.
Lycosid spiders have 13 pairs of telocentric chromosomes and 2 nonhomologous sex chromosomes in males. At leptotene, the kinetochore ends are attached to the nuclear envelope via thickened attachment plaques. Homologous synapsis begins at the attachment plaques and proceeds zipper-like through the length of the synaptonemal complex. We have tested whether or not this simple form of homologous synapsis is obligatory by inducing reciprocal translocations. Since we find many irradiated cells with quadrivalents at diakinesis-prometaphase and metaphase I, clearly a backup system exists that can bring together homologous segments disparate from each other in the nucleus. This mechanism apparently does not depend on end-initiated synapsis. Furthermore, we have found in previous studies that wolf spider bivalents are always unichiasmate, with either proximally or distally placed chiasmata. Since many chain quadrivalents, but no ring quadrivalents, were seen in this study, crossing over and chiasma placement obey a different set of rules when homologous segments are switched between chromosomes.
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Change in memory performance and its correspondence to change in speed of performance and self-reported memory functioning were investigated longitudinally in 30 older adults with memory complaints. Subjects were assessed by self-report questionnaires and cognitive tests 3 times, at near 2-year intervals. A significant decline in word-recall scores was found, which was accompanied at the group level by significant self-reported decline in everyday memory functioning and nonsignificant decline in Wechsler Adult Intelligence Scale Digit Symbol scores (alpha = .05). The oldest subjects showed the most substantial declines in memory performance. At the individual level, however, memory change did not significantly correlate with either change in self-reports or change in Digit Symbol scores. Although these results do not support a cognitive slowing model of decline at the intraindividual level, they do have implications for intervention of age-related memory decline.
OBJECTIVES: Describe an outbreak of influenza A (H3N2); provide an analysis of vaccine efficacy; measure the sensitivity, specificity, and positive predictive value of 3 clinical case definitions of influenza. SETTING: A nursing home in Washington County, Maryland. The outbreak involved 52 residents (attack rate = 47.7%) and at least 10 of 140 employees (minimum attack rate = 7.1%). RESULTS: Twenty-five residents exhibited a 4-fold or greater increase in titer to influenza A/Sichuan/2/87. Vaccine efficacy was measured at -7.1%, suggesting that the influenza vaccine in 1988/1989 did not offer optimal protection against influenza A infection for the institutionalized elderly. CONCLUSIONS: The outbreak was a clear indicator of the need for rapid diagnosis. With the use of rapid diagnostic tests, influenza A could have been detected in time to use amantadine.
1. The depression in axonal excitability that follows short trains of impulses (H1) may lead to spike frequency adaptation to a sustained stimulus, and has been attributed to a slow K+ conductance. The present experiments sought indirect evidence for slow K+ channels at the node of Ranvier of human cutaneous afferents based on the demonstration of post-tetanic changes in excitability typical of H1. 2. The excitability changes in low-threshold cutaneous afferents in the digital nerves of the index finger were explored using a submaximal test pulse conditioned by trains of supramaximal stimuli, containing up to 100 impulses. Changes in the amplitude of the compound sensory action potential set up by a constant test stimulus were used as a measure of the changes in excitability. These changes in amplitude were paralleled by inverse changes in latency. 3. When the conditioning stimulus was a single supramaximal pulse, excitability was enhanced at conditioning-test intervals of 4-40 ms, with a peak at 6-8 ms. When the conditioning stimulus consisted of a train of ten pulses delivered at 200 Hz, the recovery cycle was dominated by subnormality that was maximal at 20 ms and subsided gradually over 50 ms. 4. The post-train depression in excitability increased as the number of pulses in the conditioning train increased to ten but changed little with further increases in train duration. The degree of depression increased with the pulse frequency within the train. Cooling the hand from a skin temperature of 35 to 25 degrees C slowed the recovery processes but did not alter the magnitude of the post-train depression. 5. These characteristics are typical of the H1 phase of post-tetanic depression in axonal excitability. The extent of the depression in excitability suggests, first, that there may be a significant K+ conductance at the nodes of human cutaneous afferents and, secondly, that H1 may play a significant role in limiting repetitive discharge in normal and pathological afferents.
1. It has been demonstrated that subjects can alter the reflex stiffness of the elbow and wrist in response to imperceptibly slow perturbations applied through a complaint coupling. We used this technique to measure ankle stiffness in standing subjects as a means of examining reflex activity. 2. During unperturbed stance, a linear relationship between ankle torque and ankle angle is expressed as a load stiffness. The load stiffness predicted from a subject's measured physical dimensions corresponds closely with the value measured by standing the subject on a force platform. 3. Slow perturbations were applied at waist level, through a spring, to standing subjects. The perturbations caused sway similar in magnitude and rate to the sway of normal stance. Ankle stiffness was measured during the period when the perturbations were unperceived. The contribution to ankle stiffness of reflexes that use visual information was assessed by eye closure. The ability of reflexes based on sensory information from the legs to maintain upright posture was assessed when subjects balanced a load equivalent to their own body, in a situation where neither visual nor vestibular information could assist. Ankle stiffness was measured while the load was perturbed. 4. The results show that a simple mechanical model of stance predicts the torque-angle relationship at the ankle. This relationship determines the minimal ankle stiffness required to stand, and reflex muscle stiffness is a necessary component of this ankle stiffness. Visual, vestibular and lower limb sensorimotor reflexes each contribute to ankle stiffness; however, the local sensory reflexes alone are sufficient to stand. For responses to unperceived perturbations, standing subjects can alter their reflex ankle stiffness according to intentional set.
1. Subjects' ability to detect movements imposed at the elbow during active flexion was measured. Movements of three different angular velocities (0.04, 0.4 and 4.4 deg/s) were applied to the arm while subjects maintained one of two force levels of active flexion. The threshold magnitudes for detection of the direction of imposed movement were found. 2. All thresholds were very small. At the lowest velocity of movement the average threshold was 0.13 deg and no subject had a threshold of greater than 0.3 deg. This contrasts with thresholds of over 2 deg measured in a previous study when the muscles about the joint were relaxed. Thresholds decreased further with increasing velocity of movement. 3. No difference was found between the two levels of contraction of the elbow flexors. However, extension (stretch of the contracting muscle) and flexion thresholds were calculated separately, and smaller extensions than flexions could be detected. 4. These findings indicate that conscious detection of imposed movements is greatly enhanced during active muscle contraction. Movements which cause unloading of the contracting agonist, as well as movements which result in stretch, are more easily detected than when the muscle is contracting. The discussion focuses on possible mechanisms for this enhancement.
Corneal cell cultures were established from the corneas of rabbits killed during a period of latency 118 d after ocular infection with the RE strain of herpes simplex virus (HSV). DNA was isolated from frozen cell pellets of 42 cell cultures that did not develop viral cytopathic effects during 44 d in culture. Using the polymerase chain reaction (PCR) to amplify HSV thymidine kinase (TK) gene sequences, HSV-specific DNA was detected in 15 of 42 culture-negative cell cultures. Subsequent reamplification, using nested primers that were complementary to HSV TK sequences internal to the orginal primers, resulted in eight additional culture-negative samples showing positive hybridization for HSV TK DNA. Twenty three of the 42 virus culture-negative corneal cell cultures tested by PCR were found to contain HSV genetic material. Detailed examination of the clinical histories of the eyes from which the corneal cultures were obtained showed no correlation between increased frequency or severity of epithelial disease, stromal disease, or virus shedding and more frequent isolation of virus or detection of HSV-specific DNA. These studies document that HSV DNA residues in the corneas of HSV-infected rabbits up to 118 d post-infection. About 10% of the eyes contained virus that could be reactivated in culture, whereas an additional 55% of the eyes contained DNA sequences homologous to a portion of the HSV TK gene.
Seventeen patients with breast cancer underwent preoperative radioimmunoscintigraphy (RIS). Planar and tomographic imaging techniques (single photon emission computerised tomography--SPECT) were studied using Indium-111-labelled anti-epithelial membrane antigen (EMA) antibodies for tumour localisation. Overall imaging sensitivities were reasonable with correct identification of around 90% of primary lesions and 50% of secondary lesions. Planar imaging was more sensitive than SPECT for identification of superficial lesions such as the primary lesions (88% vs 56%) and axillary metastases (59% vs 53%). SPECT was necessary, however, for detection of deeper lesions such as internal mammary chain metastases and often served as an adjunct rather than an alternative to planar imaging. RIS, therefore, may contribute to more accurate staging of breast cancer, although further technical advances in RIS would enhance this contribution.
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.
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.
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.
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.
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)
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.
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.