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Biomedical subjects

W L Thompson

Publications and source records attributed to W L Thompson.

At least 37 records · Page 2Linked to original sources
PubMed1995

The distribution of [125I]ricin in mice following aerosol inhalation exposure.

Studies were conducted to examine the uptake and redistribution of [125I]ricin from the lungs of mice following nose-only aerosol inhalation exposure. Radiolabelled contents were measured in lung and various extra-pulmonary tissues 15 min through 30 h following 10 min aerosol exposures. Pharmacokinetic analyses were performed on whole-organ data obtained for lungs, stomach, liver and spleen. Radioactivity within the lungs, maximal at 15 min post-exposure, was eliminated in a biexponential fashion with a long beta half-life (approximately 40 h). Large amounts of radiolabel were also found within the gastrointestinal tract. Radiolabel within the stomach exhibited an absorption phase and two-compartment elimination. Radiolabel content of many other tissues, including known accumulation sites for intravenously administered toxin, was significantly (p < 0.05) increased (relative to 15 min post-exposure) in association with the early elimination of radiolabel from the lungs, but levels in these tissues were very low and did not increase after 4 h post-exposure. The only exception was our sample of trachea, which showed delayed elevations in radiolabel (peak at 24 h); this pattern was attributable to the contained thyroid (not removed at necropsy) and its trapping of free [125I] released upon tissue [125I]ricin degradation. The overall data indicate that ricin administered by aerosol inhalation is delivered to both respiratory and gastrointestinal tracts; however, it is not extensively transported from either tract to other potential target sites. Ricin delivered to the lungs is primarily sequestered within the lungs until degradation. Only small amounts of ricin delivered to the gastrointestinal tract are absorbed into the circulation.

Administration, Inhalation↗
PubMed1995

Drugs that show protective effects from ricin toxicity in in vitro protein synthesis assays.

We used an in-vitro, inhibition of protein synthesis assay (PSI) to test a wide variety of drugs for possible therapeutic use against ricin, a toxic glycoprotein that causes death in animals by inhibiting protein synthesis. Selection of test drugs was based on possible interference with ricin activity at different stages of the toxic process. Most of the drugs tested had no effect on ricin-induced PSI, were toxic when tested alone, or enhanced the toxicity of ricin. The only ones showing protection were galactose, lactose, and several derivatives of these sugars, Brefeldin A (BFA), 3'-azido-3'-deoxythymidine (AZT), and a purine derivative (BM33203). THe sugar derivatives provided 50% protection against a PSI ED99 of ricin (0.1 micrograms/ml). Concentrations of BFA greater than 0.5 micro M caused about 50% PSI by itself, but blocked any further inhibitory effects of ricin. AZT, at optimum concentrations, reached a maximum protection level of about 40% in the presence of an ED99 dose of ricin, while the nucleoside derivative, BM33203 and AZT appeared to have an additive effect, showing up to 80% protection from an ED99 dose of ricin. Drugs showing protection in the PSI cell assay showed no protection from ricin in a cell-free translation assay used to determine if they would block ricin at the protein synthesis site.

Animals↗
PubMed1995

Reactivity of magnetic parieto-occipital alpha rhythm during visual imagery.

Spontaneous MEG signals were recorded during visual imagery from 13 healthy adults with a whole-scalp neuromagnetometer. The parieto-occipital 7-14 Hz alpha activity was suppressed strongly while subjects visualized and evaluated letters. The act of forming a visual image caused a smaller suppression than did inspection of the imaged pattern for a named property. The maximum suppression depended on the baseline alpha level and, for the majority of the subjects, occurred close to the area with the strongest alpha, showing no systematic hemispheric asymmetry. Sources for the alpha activity, modeled with equivalent current dipoles, clustered in the parietal and occipital lobes. The strongest suppression of the activity occurred near the parieto-occipital sulcus.

Adult↗
PubMed1995

Two types of image generation: evidence for left and right hemisphere processes.

The results from seven experiments provide evidence that visual mental images can be generated by either the left or right cerebral hemisphere, but in different ways. Subjects were cued to form images within a grid or within a set of four corner brackets; a single X mark was enclosed within each stimulus, and the subjects were to determine whether the X mark was enclosed within each stimulus, and the subjects were to determine whether the X mark would have fallen on an imaged pattern. When subjects memorized descriptions of how parts were arranged, they could later form images of the composite pattern when cued in the right visual field (left hemisphere) more accurately than when they were cued in the left visual field (right hemisphere). In contrast, when subjects memorized individual segments on a screen, and 'mentally glued' them into a single pattern, they later could form images more accurately, at least in some circumstances, when cued in the left visual field. These results were predicted by the theory that images are built up by arranging parts, and that two different processes can be used to arrange them. One process uses stored descriptions to arrange parts, and is more effective in the left cerebral hemisphere; the other process uses stored memories of metric positions to arrange parts, and is more effective in the right cerebral hemisphere. Convergent evidence was obtained by having subjects memorize letters in grids (which are easily encoded using descriptions of the positions of segments) or within a space delineated by four brackets (which require memorizing the precise positions of the segments). Subjects were relatively more accurate when cued in the left visual field with bracket stimuli, but tended to be relatively more accurate when cued in the right visual field with grids stimuli. Control experiments showed that this finding was not due to hemispheric differences in the ease of forming images at different sizes or differences in the ease of perceptually encoding the probes.

Adolescent↗
PubMed1994

Characterization of 3'-azido-3'-deoxythymidine inhibition of ricin and Pseudomonas exotoxin A toxicity in CHO and Vero cells.

Ricin (RIC), modeccin (MOD), Pseudomonas exotoxin A (PE), and diphtheria toxin (DT) are protein toxins that enter cells by receptor-mediated endocytosis. After intracellular transport and membrane translocation to the cytosol, these toxins inhibit protein synthesis by enzymatically removing a specific adenine residue from ribosomal RNA (RIC, MOD), or by ADP-ribosylation of elongation factor-2 (PE, DT). Recently, Thompson and Pace (1992) reported that AZT (3'-azido-3'-deoxythymidine) inhibited RIC toxicity in Vero cells, and this inhibition was not due to a block of RIC enzymatic activity. This paper extends these findings and examines the effects of AZT treatment on the toxicities of other protein toxins in Chinese hamster ovary (CHO) and Vero cell lines. AZT treatment did not significantly alter the toxicity of DT or MOD in either cell line, but it markedly reduced RIC and PE toxicity in both cell lines. The ID50 values (concentration of toxin required to inhibit protein synthesis by 50%) for RIC and PE in CHO cells increased approximately 6.5- and 12.5-fold, respectively; while in Vero cells the ID50 values increased ca. 8.5- and 4.5-fold, respectively. Results of further studies revealed differences in the mechanisms by which AZT inhibited RIC and PE toxicity. Results of cell-free translation indicated that, unlike its effects on RIC, AZT blocked the ability of PE to perform its enzymatic activity. As AZT did not block RIC enzymatic activity, we examined the effects of AZT on earlier steps in the RIC intoxication process. AZT treatment did not inhibit cell-surface binding or internalization of [125I]-RIC. Results of kinetic studies showed that when AZT was incubated with cells at the time of RIC exposure, it caused no major change in the lag phase, during which RIC reaches the site of translocation. However, it clearly reduced the subsequent first-order reduction in the rate of protein synthesis, suggesting an effect on translocation. Monensin (an ionophore that perturbs intracellular trafficking and increases the toxicities of RIC and PE) reduced AZT protection against both toxins. Nocodazole and colchicine (agents that disrupt microtubules and some routes of intracellular trafficking) reduced the ability of AZT to inhibit RIC, but not PE, toxicity. In summary, our results suggest that (1) AZT acts within the cytosol to inhibit (directly or indirectly) the enzymatic action of PE, and (2) the AZT inhibition of RIC cytotoxicity does not involve perturbations of RIC cell-surface binding, internalization, or enzymatic activity but might result from an alteration in RIC translocation.

ADP Ribose Transferases↗
PubMed1994

Identifying objects seen from different viewpoints. A PET investigation.

Positron emission tomography scans were acquired when subjects performed three tasks, each in a separate block of trials. They decided whether words named pictures of objects viewed from a canonical perspective, decided whether words named pictures of objects viewed from a non-canonical (unusual) perspective or saw random patterns of lines and pressed a pedal when they heard the word (this was a baseline condition). The dorsolateral prefrontal region was activated when subjects identified objects seen from non-canonical perspectives, as expected if the frontal lobes are involved in top-down perceptual processing. In addition, several areas in the occipital, temporal and parietal lobes were selectively activated when subjects identified objects seen from non-canonical perspectives, as specifically predicted by a recent theory. Overall, the pattern of results supported the view that the human brain identifies objects by using a system of areas similar to that suggested by studies of other primates.

Adolescent↗
PubMed1990

In vivo effects of T-2 mycotoxin on synthesis of proteins and DNA in rat tissues.

Rats were given an ip injection of T-2 mycotoxin (T-2), the T-2 metabolite, T-2 tetraol (tetraol), or cycloheximide. Serum, liver, heart, kidney, spleen, muscle, and intestine were collected at 3, 6, and 9 hr postinjection after a 2-hr pulse at each time with [14C]leucine and [3H]thymidine. Protein and DNA synthesis levels in rats were determined by dual-label counting of the acid-precipitable fraction of tissue homogenates. Rats given a lethal dose of T-2, tetraol, or cycloheximide died between 14 and 20 hr. Maximum inhibition of protein synthesis at the earliest time period was observed in additional rats given the same lethal dose of the three treatments and continued for the duration of the study (9 hr). With sublethal doses of T-2 or tetraol, the same early decrease in protein synthesis was observed but, in most of the tissues, recovery was seen with time. In the T-2-treated rats. DNA synthesis in the six tissues studied was also suppressed, although to a lesser degree. With sublethal doses, complete recovery of DNA synthesis took place in four of the six tissues by 9 hr after toxin exposure. The appearance of newly translated serum proteins did not occur in the animals treated with T-2 mycotoxin or cycloheximide, as evidenced by total and PCA-soluble serum levels of labeled leucine. An increase in tissue-pool levels of free leucine and thymidine in response to T-2 mycotoxin was also noted. T-2 mycotoxin, its metabolite, T-2 tetraol, and cycloheximide cause a rapid inhibition of protein and DNA synthesis in all tissue types studied. These results are compared with the responses seen in in vitro studies.

Amino Acids↗
PubMed1990

Distribution and elimination of brevetoxin PbTx-3 in rats.

After i.v. administration, [3H]PbTx-3 was rapidly cleared from the blood; less than 10% remained after 1 min. Within 30 min, radiolabel distributed to skeletal muscle (69.5%), liver (18.0%), and intestinal tract (8.0%). Over 24 hr, radiolabel decreased in muscle, remained constant in liver, and increased in the intestinal tract and feces. Elimination occurred via feces (75.1%) and urine (14.4%), with 9.0% remaining in the carcass after 6 days. This distribution and elimination profile suggested that the liver was the major organ of metabolism and that biliary excretion was an important route of elimination. Thin-layer chromatography confirmed the presence of brevetoxin metabolites in fecal extracts. Skeletal muscle does not appear to be a site of metabolism, but a storage compartment, from which toxin is slowly released prior to clearance by the liver. These studies are the first demonstration of in vivo brevetoxin metabolism in mammals.

Animals↗
PubMed1990

Taking care of culturally different and non-English speaking patients.

Many physicians evaluate and care for non-English speaking patients and patients from different cultures. If not carefully considered, cultural factors, including language, often interfere with optimal diagnosis and treatment of these patients. In addition to improved clinical care, increased awareness and assessment of these issues will often enhance patient and family satisfaction and cooperation with therapeutic recommendations. A number of cultural examples are given to illustrate various points, which of course cannot be comprehensive, but which should alert the physician for areas to focus upon. The knowledge and skills to perform a sociocultural differential diagnosis and to initiate treatments in these areas are especially important for consultation-liaison psychiatrists.

Cross-Cultural Comparison↗
PubMed1989

Clinical pharmacokinetics of pinacidil, a potassium channel opener, in hypertension.

Pinacidil is a potassium channel opener that decreases blood pressure by reducing peripheral arterial resistance. In two multicenter trials, we studied the concentrations and apparent clearance of pinacidil (406 patients) and concentrations of its pyridyl-N-oxide metabolite (147 patients). Responding patients had plasma samples collected hourly for 12 hours on 2 occasions after weeks to months of treatment. Pinacidil dose was titrated from 12.5 to 75 mg b.i.d. The peak concentration of pinacidil and N-oxide and the area under the concentration-time curve (AUC) were proportional to the dose of pinacidil, with an average pinacidil concentration of 268 micrograms/L (1.02 microM) and N-oxide concentration of 172 micrograms/L (0.65 microM) for every 1 mg/kg pinacidil administered. Clearance of pinacidil (Clp = Dose/AUC) was 31 L/hr in patients younger than 45 years and 27 L/hr in those older than 60. Clp was significantly smaller in white patients compared with other races (Clp = 28 vs. 34 L/hr). Clp was significantly less in patients taking hydrochlorothiazide (27 vs. 31 L/hr) and greater in smokers (33 vs. 29 L/hr). Concomitant propranolol use did not influence Clp.

Adult↗
PubMed1989

Coronavirus-like particles in adults in Melbourne, Australia.

Coronavirus-like particle(s) (CVLP) are faecal-derived pleomorphic membrane bound virus-like particles characterised by a fringe of club-shaped spikes that measure about 27 nm in length. The association of CVLP with a variety of social, clinical, and epidemiological factors was examined after a 69 month survey of faeces received for routine testing at an infectious diseases hospital. CVLP was found most commonly in three groups: first, intellectually retarded individuals who were usually inmates of institutions; second, recent overseas travellers who were either Indochinese refugees/immigrants or were overseas travellers who had usually visited developing communities for lengthy periods; and, third, male homosexuals who had a history of multiple sexual contacts and/or venereal disease. It was concluded that the excretion of CVLP had a strong association with unhygienic living or working conditions irrespective of any clinical symptoms the individual might show.

Adolescent↗
PubMed1989

Use of fluoxetine, a selective serotonin-uptake inhibitor, in the treatment of obesity: a dose-response study (with a commentary by Michael Weintraub).

Pharmacologic measures which increase serotonergic activity in the brain decrease food consumption and lead to decreased weight in animals. Fluoxetine, an inhibitor of serotonin reuptake, decreases food intake in animals and is associated with weight loss in depressed and otherwise healthy obese patients. To determine the most effective daily fixed dose which causes weight loss in nondepressed obese patients, fluoxetine (10, 20, 40 or 60 mg) or placebo was administered once daily for 8 weeks to 655 patients consisting primarily of women (mean age 40 years, mean weight 95 kg). Diet and activity were not controlled. The placebo-treated patients lost 0.6 +/- 2.3 kg. With the 60-mg fluoxetine dose, patients lost an average of 4.0 +/- 3.9 kg (P less than 0.001), with intermediate responses at the lower doses. Weight loss was proportional to the initial body mass index (weight/height squared). There were no statistically significant differences between any fluoxetine treatment group and placebo for discontinuations from the study. There were statistically significant dose-dependent increases in reports of asthenia, somnolence and sweating. Thus, fluoxetine 60 mg daily appears to be potentially effective for use in weight reduction.

Adolescent↗
PubMed1989

Beneficial effects of pinacidil on blood lipids: comparisons with prazosin and placebo in patients with hypertension. Pinacidil-Prazosin and Pinacidil-Placebo Research Groups, Lilly Research Laboratories.

In two randomized, double-blind clinical trials comparing pinacidil with prazosin and with placebo in patients with hypertension, a number of statistically significant and potentially beneficial effects on blood lipids were detected in the patients taking pinacidil. Patients treated with pinacidil exhibited significant average decrements from baseline in concentrations of total and low-density lipoprotein cholesterol and triglycerides and a significant average increment in high-density lipoprotein cholesterol. The mean effects seen in the pinacidil group were significantly greater than those in the placebo group for both total cholesterol (-9.8 vs +4.2 mg/dl, p less than 0.001) and triglycerides (-21.6 vs +8.6 mg/dl, p less than 0.001). The effects seen in patients given pinacidil were also significantly greater than those seen in the patients treated with prazosin for both high-density lipoprotein cholesterol (+3.6 vs -1.0 mg/dl, p = 0.002) and triglycerides (-14.8 vs +30.3 mg/dl, p less than 0.001). Negative effects of hydrochlorothiazide and propranolol on blood lipids were not apparent in patients given pinacidil. Thus, pinacidil treatment of hypertension is associated with a beneficial effect on blood lipids, which may be of clinical significance.

Antihypertensive Agents↗
PubMed1988

Vasodilator monotherapy in the treatment of hypertension: comparative efficacy and safety of pinacidil, a potassium channel opener, and prazosin.

We compared antihypertensive effects of monotherapy with pinacidil (N = 197) or prazosin (N = 204) in a randomized, parallel, double-blind dose-titration study in which hydrochlorothiazide or propranolol could be added for adverse events or lack of efficacy. Pinacidil (12.5 to 75 mg b.i.d.) was a more potent vasodilator, producing a mean decrease in supine diastolic blood pressure (baseline = 102 to 103 +/- 9 mm Hg) of 18.8 +/- 10.0 (SD) mm Hg compared with 15.5 +/- 9.2 mm Hg with prazosin (1 to 10 mg b.i.d.; p less than 0.001). Patients responding to each drug had similar average blood pressure levels during 12-hour monitoring (137/85 mm Hg). More patients taking pinacidil required hydrochlorothiazide for edema (p = 0.008) and more taking prazosin required hydrochlorothiazide and propranolol for lack of efficacy (p less than 0.001). Tachycardia (15% to 20%) and palpitation (13% to 15%) were frequent events with both drugs. Edema (38.2% vs 22.3%) was more frequent with pinacidil (p less than 0.001) and postural hypotension (4.7% vs 1.0%) and asthenia (20.2% vs 13.2%) were more frequent with prazosin (p = 0.025; 0.062). No significant laboratory toxicity was noted. In conclusion, both pinacidil and prazosin are effective as monotherapy for hypertension. Monotherapy with pinacidil is limited by adverse events related to vasodilatation and monotherapy with prazosin is limited by lack of efficacy.

Adult↗