Mexiletine-theophylline interaction.
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Aged↗
Biomedical subjects
J L Taylor
Publications and source records attributed to J L Taylor.
Synergistic antiherpes virus activity of acyclovir and interferon in human corneal stromal cells.
Synergistic anti-herpes simplex virus type 1 (HSV-1) activity between acyclovir (ACV) and recombinant human interferon alpha A2 (IFN) was detected in cell cultures derived from human corneas. This activity was demonstrated when cells were infected at high multipicities of infection (5 pfu/cell) in both cytopathic effect reduction and yield reduction assays as well as in plaque reduction assays at low multiplicities. The synergistic effects occurred over a 30-fold range of concentrations of IFN (6-200 IU/ml) and ACV (0.15-5 microM) at various ratios of the drugs. The augmentation of antiviral activity was greatest when cells were treated with IFN prior to infection and ACV following infection. The addition of IFN after infection, with simultaneous ACV treatment, also resulted in enhanced anti-HSV-1 activity. The combination of IFN with ACV did not increase the cytotoxicity of ACV. The synergistic antiviral activity in corneal cells may account for the previously reported enhanced efficacy of combined treatment with IFNs and nucleoside analogs for therapy of herpetic keratitis.
Acyclovir↗
The isolation of herpes simplex virus from rabbit corneas during latency.
Herpes simplex virus type 1 (HSV-1) latency, as operationally defined, is a state in which cell-free infectious virus cannot be demonstrated in tissue at the time of sacrifice, but infectious virus can be isolated from the same tissue after prolonged cultivation. Latent HSV has been routinely detected in sensory ganglia of the infected dermatome. We have isolated HSV-1 (RE) from the corneas of 11% of infected rabbits which harbored virus in a latent state in trigeminal ganglia. HSV-1 (RE) was isolated from 10 of 88 cultures of corneal cells established following collagenase digestion of individual corneas taken from asymptomatic animals 118 days after infection. Virus was recovered only after prolonged primary culture and in some cases serial passage of corneal cells (range 5 to 26 days to initial cytopathic effect, n = 10). Virus was isolated from 68 of 68 trigeminal ganglia from the same rabbits by cocultivation of ganglion pieces with Vero cells (range 9 to 20 days to initial cytopathic effect, n = 68) while no cell-free virus was isolated from ganglia at the time of sacrifice. Virus isolation from corneas during the latent period occurred in a manner independent of prior antiviral or antiviral plus immunosuppressive therapy. Clinical evaluation of the corneas throughout the course of acute disease, stromal disease, and at the time of sacrifice provided no evidence that could be used to predict which corneas would yield virus. These data suggest that HSV-1 can remain in a nonreplicative state characteristic of latency in cells of rabbit corneas for long periods after infection and therapy of herpetic eye disease.
Animals↗
Antiviral and antidifferentiative activities of interferon beta and gamma in relation to their induction of double-stranded RNA-dependent protein kinase activity in 3T3-L1 cells.
Mouse interferons beta (IFN-beta) and gamma (IFN-gamma) inhibit the differentiation of 3T3-L1 fibroblasts into adipocytes when added to cultures at the time of induction of differentiation. Differentiation, as measured by incorporation of radiolabeled leucine into lipids, was inhibited 50% by approximately 1-3 units/ml of either IFN-beta or IFN-gamma, with maximum inhibition of differentiation achieved with 100 units/ml of either IFN. The magnitude of antiviral activity induced by IFN-beta and IFN-gamma was similar in differentiated and undifferentiated 3T3-L1 cells, although the slopes of the dose-response curves were different; IFN-gamma induced an antiviral state with greater efficiency than IFN-beta in differentiated and undifferentiated 3T3-L1 cells. By contrast, IFN-beta induced the double-stranded RNA-dependent P1 protein kinase more efficiently than did IFN-gamma in both differentiated and undifferentiated cells. However, IFN-beta and IFN-gamma both induced greater phosphorylation of protein P1 in cell-free extracts prepared from differentiated adipocytes than in extracts from undifferentiated fibroblasts. Cultures treated with either beta or gamma IFN throughout 8 days of differentiation continued to produce double-stranded RNA-dependent protein kinase in a manner dependent on IFN dose. These results suggest that the antiviral and antidifferentiative activities of IFN-beta and IFN-gamma in 3T3-L1 cells involve different molecular mechanisms.
1-Methyl-3-isobutylxanthine↗
Cortical blindness after left internal mammary artery to left anterior descending coronary artery graft angiography.
We describe a case of transient cortical blindness following internal mammary artery to left anterior descending coronary artery graft angiography. This dramatic, infrequent, and self-limiting complication so far has not been described in the cardiovascular literature. In the present era of internal mammary artery use for the left coronary artery grafting, the angiographer should be familiar with the diagnosis, prevention, and management of complications previously seen mostly during the posterior cerebral circulation angiography.
Angiography↗
Proprioception in the neck.
Proprioception in the neck was investigated in normal human subjects. Three experiments studied rotation of the head about a vertical axis on the body. Accuracy of pointing, thresholds for detection of passive movement, and control of fine movement were tested. Comparison of the accuracy of pointing at the big toe with the nose and with the arm, showed a smaller scatter of angular misalignments when pointing with the arm. However, the arm pointed systematically off target. Pointing at the target toe by turning the head was not significantly more accurate than aligning the nose and toe by turning the chair and body with the head fixed. The highest threshold found for the detection of the direction of passive movement of the head relative to the body was 1.4 degrees angular displacement. Thresholds were highest at the slowest angular velocity and dropped as angular velocity increased. When the head was turned on the body thresholds were lower than when the body was turned and the head held still. Control of fine angular movements of the head and of the distal phalanx of the right thumb were compared by measuring subjects' accuracy in guiding a cursor through a path on a computer screen by turning the head or moving the thumb. The thumb was found to be better controlled than the head.
Humans↗
Pointing.
The roles of vision and proprioception in the task of pointing at a distant object were investigated. When guided solely by proprioception, subjects pointed from the shoulder through the finger to the object, down the long axis of the arm. When vision was present, it dominated proprioception and subjects pointed with the fingertip close to a sight line from the eyes to the object.
Cues↗
A study of somatic complaints and psychiatric diagnosis in children.
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Abdomen↗
A comparison of assessment techniques measuring the effects of methylphenidate, secobarbital, diazepam and diphenhydramine in abstinent alcoholics.
In two studies, we studied the comparative sensitivity of different subjective and objective measures to methylphenidate (10 and 20 mg) and secobarbital (100 mg) versus placebo, and diphenhydramine (50 mg) and diazepam (10 and 20 mg) versus placebo in abstinent alcoholics. Subjective measures used were the Visual Analog Mood Scale and the Profile of Mood States. Objective measures were the Stroop and two microcomputer-controlled tasks developed in our lab - a dual pursuit tracking/reaction time task (P-Trak) and a reaction time task with regular and irregular preparatory intervals (PI) of varying length (Reactest). In addition, several baseline measures (Eysenck Personality Inventory, Spielberger State-Trait Anxiety Inventory and NIMH Mood Scale Elderly) were evaluated for their correlation to drug response. All three central nervous system depressants impaired performance on Reactest at the longer PIs and showed a main effect with irregular PIs, but only the 20-mg dose of diazepam impaired reaction time at the shortest PI and showed a main effect with regular PIs. On P-Trak, secobarbital and diazepam 20 mg impaired both tracking and reaction time, while methylphenidate 20 mg improved only the reaction time component. Only diazepam 20 mg affected mood. No effects were noted on the Stroop. The implications of these findings are discussed. Both P-Trak and Reactest with long PIs were more sensitive than VAMS, POMS or Stroop to drug effects. As lower doses of central nervous system depressants impaired reaction time only with longer PIs and showed a main effect only with irregular PIs, cognitive effects of these drugs may be missed if only subjective or short, regular PI tasks are examined.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Adenosine deaminase in herpes simplex virus induced corneal stromal disease.
The development of herpes simplex virus (HSV)-induced disciform stromal disease produced by the intrastromal injection of the RE strain of HSV-1 is characterized by concurrent increases in adenosine deaminase (ADA) activity and corneal thickness. ADA activity increased from 8.6 units/cornea in normal corneas to about 14.1 units and 31.1 units in mock-infected controls and HSV-infected corneas respectively by 15 days postinjection. The molecular weight species of ADA in the corneas of HSV-infected rabbits appeared altered relative to that present in corneas which were not infected. A single topical dose with as low as 0.1% 2'-deoxycoformycin (dCF), an ADA inhibitor possessing immunosuppressive activity, was capable of totally inhibiting the corneal ADA activity. Titration of the free dCF in the cornea following a single topical dose of 0.25% dCF indicated that enough dCF remained in the cornea 24 hrs after instillation to totally inhibit all corneal ADA plus 66 units of additional enzyme. These data suggest that ADA may be a suitable target for immunosuppressive therapy during HSV-induced disciform stromal disease.
Adenosine Deaminase↗
The antiherpesvirus activity and cytotoxicity of sangivamycin.
Sangivamycin, 4-amino-5-carboxamido-7-(beta-D-ribofuranosyl)-pyrrolo[2,3-d]-pyrimidine is a structural analog of adenosine belonging to a group of nucleosides classified as pyrrolopyrimidines. Sangivamycin, an adenosine deaminase resistant analog, was found to inhibit the replication of three strains of herpes simplex virus type 1 (HSV-1) by 50% (ED50) at a concentration approximately equal to the concentration which inhibits cell growth by 50% (LD50). Both Vero cells and rabbit corneal stromal cells in exponential growth were about 10-fold more sensitive to the drug than quiescent cells. The selectivity indices of sangivamycin indicated that the drug was not a highly selective antiviral agent and, therefore, would offer no advantage over drugs currently available for the treatment of herpetic keratitis.
Animals↗
Interferon production in inbred mice during herpetic eye disease.
Low levels (less than 5 units/eye) of interferon (IFN) were detected in the eyes of BALB/c and C57BL/6 mice one to five days after instillation of 10(7) pfu/eye of herpes simplex virus type 1 (HSV) onto scarified corneas. This dose of virus produced herpetic keratitis characterized by dendritic epithelial lesions one day post infection in both strains of mice. The disease progressed to severe necrotizing stromal keratitis in the eyes of all BALB/c mice, but only three of 10 eyes of C57BL/6 mice by 21 days after infection. Footpad immunization 30 days prior to ocular infection protected both strains from stromal disease, but did not enhance IFN production in the eye. At lower inoculating doses of virus (less than or equal to 10(5) pfu/eye), C57BL/6 mice showed greater resistance to stromal disease and produced less virus over a shorter period of time than BALB/c mice. No IFN was detected at any time after infection with doses of virus less than 10(7) pfu/eye, nor was IFN detected in plasma of any infected mice. The failure to detect high levels of IFN in homogenates of eyes did not reflect an inability of ocular tissues to produce IFN since IFN-beta was detected as early as two hours after topical treatment with the potent IFN inducer, carboxymethylacridanone (CMA). The two mouse strains produced similar levels of IFN in the eye in response to CMA. These data indicated that the relative resistance of mice to HSV eye infection was not related to the rapid local production of IFN, nor was resistance related to systemic IFN production in plasma or spleen.
Animals↗
Splenic conservation and the management of splenic artery aneurysm.
We report two patients with splenic artery aneurysm diagnosed by CT, treated by proximal and distal ligation of the splenic artery and followed for two years by CT to assess splenic size and pitted erythrocyte counting to assess function. Literature review shows that excision of the aneurysm and splenectomy is usual but with growing regard for conservation of splenic tissue we suggest that proximal and distal ligation of the artery is a preferable alternative as shown by splenic function tests in these patients.
Aneurysm↗
Herpetic keratitis in experimental vitamin A deficiency.
Herpes simplex virus type I (KOS) was instilled onto the eyes of rabbits with experimentally induced xerophthalmia (vitamin A deficient) and control animals fed a vitamin A supplemented diet. The severity of the herpes virus-induced corneal disease, assessed by biomicroscopic examination and by counting the number of corneal lesions as well as by determining the virus titers, was significantly less in vitamin A deficient animals than in controls. Infection of the corneas of the vitamin A deficient rabbits with herpes simplex virus did not precipitate keratomalacia. The few lesions present on the corneas of the vitamin A deficient animals were in the corneal periphery, which was less keratinized than the central cornea. Electron microscopy suggested that virus was capable of replicating in the basal and wing cells in the peripheral corneal lesions in the vitamin A deficient animals. These studies indicate that vitamin A deficiency alone may not predispose the host to more severe ocular herpesvirus infections.
Acute Disease↗
Acute myocardial infarction in a patient with anomalous right coronary artery.
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Aged↗
Annual cycles of plasma and testicular androgens in the lizard Tiliqua (Trachydosaurus) rugosa.
Androgen production during the annual reproductive cycle was investigated in the male scincid lizard Tiliqua (Trachydosaurus) rugosa. Concentrations of testosterone and epitestosterone were measured in plasma and testis (incubated and nonincubated) using radioimmunoassay. Morphological and histological techniques were used to determine the anatomical changes in the testis. Mating behavior was observed during spring, and sperm were most numerous in the testis at this time. Histological evidence and changes in testicular weight indicated that spermatogenesis begins in autumn and culminates in spring. Testicular regression occurred soon after mating. Plasma concentrations of both androgens were maximal during spring and minimal during summer. The maximal concentrations were approximately 500 and 150 nmol/liter (epitestosterone and testosterone, respectively). The minimal plasma concentrations were 250 and 15 nmol/liter, respectively. Plasma and testicular androgen cycles followed a pattern similar to that of the spermatogenetic cycle, suggesting the possible involvement of one or both of these androgens in the control of spermatogenesis and mating behavior in these lizards.
Androgens↗
Effect of temperature on the seasonal production of testicular androgens, in vitro, by the lizard Tiliqua rugosa.
The effect of temperature on the seasonal production of testicular androgens, in vitro, was examined in the scincid lizard Tiliqua (Trachydosaurus) rugosa. Testicular tissue was incubated, in vitro, at various temperatures (18, 25, 32 and 37 degrees C). Endogenous androgens, testosterone and epitestosterone, were measured by radioimmunoassay. Epitestosterone production was maximal at 37 degrees C and minimal at 18 degrees C. There was no consistent effect of incubation temperature on testosterone production. Incubation temperature had no effect on the seasonal pattern of androgen production. The results suggest that temperature may play a part in the regulation of androgen biosynthesis in T. rugosa.
Acclimatization↗
Seasonal changes in the biochemical indices of vitamin D deficiency in the elderly: a comparison of people in residential homes, long-stay wards and attending a day hospital.
The seasonal changes in the biochemical indices of vitamin D nutrition have been measured in elderly people with differing requirements for institutionalized care. Residents of local authority homes (LAH) showed an increase in serum 25-hydroxyvitamin D3 [25(OH)D3] between spring and autumn (means 14-17 nmol/l, P less than 0.002). No significant seasonal changes were seen in patients on long-stay wards [(GW) serum 25(OH)D3 9.5 and 9.5 nmol/l] and in day-hospital attenders [(GDH) 25 and 26.8 nmol/l]. Significant differences (P less than 0.02 to P less than 0.0001) were found between the mean serum 25(OH)D3 amongst the three groups. A significant linear relationship (r = 0.84, P = 0.036) was found between mean serum 25-hydroxyvitamin D2[25(OH)D2] and dietary vitamin D2. The intake of vitamin D was suboptimal in all groups. The incidence of 25-hydroxyvitamin D deficiency [25(OH)D less than 12.5 nmol/l] varied from 11.7% of residents in LAH in autumn to 47% of GW patients in spring; but hypocalcaemia occurred less often (LAH 1.3% in autumn, GW 4.7% in spring). The diet assumes a greater role in protecting against vitamin D deficiency when the total 25(OH)D is low. Because most diets contain insufficient amounts of vitamin D, elderly institutionalized people will remain at high risk of developing vitamin D deficiency unless specific preventative measures are adopted.
25-Hydroxyvitamin D 2↗