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Biomedical subjects

E M Allen

Publications and source records attributed to E M Allen.

At least 55 records · Page 3Linked to original sources

Role of coexpression of IL-2 and herpes simplex virus proteins in recombinant vaccinia virus vectors on levels of induced immunity.

Vaccinia virus recombinants co-expressing the genes for IL-2 and HSV-1 gC or gD were used to study the potential adjuvant effects of IL-2 on immunity to HSV-1. In addition, constructs were produced which, while expressing IL-2, encoded for reduced levels of HSV-1 gC. Studies with mice revealed that gC and gD could stimulate HSV-1 immunity as measured by neutralizing antibody (NA), lymphoproliferation and viral clearance. IL-2 enhancement of NA and lymphoproliferation was observed only in those groups of mice immunized with the sub-optimal gC construct which co-expressed IL-2. In no instance did the presence of IL-2 augment the ability of mice to clear an epithelial challenge of HSV-1.

Animals↗

The effects of charcoal and sorbitol (alone and in combination) on plasma theophylline concentrations after a sustained-release formulation.

1. The effects of charcoal and sorbitol, alone and in combination, were investigated in eight healthy female volunteers who received 600 mg slow-release theophylline (two 300 mg capsules). 2. The area under the plasma concentration time curve to 24 h (AUC0-24) after theophylline alone was significantly greater than after both the charcoal and charcoal plus sorbitol phase. 3. Charcoal and charcoal with sorbitol also significantly reduced the maximum plasma theophylline concentration (Tmax) and time to maximum concentration (Cmax). 4. Sorbitol significantly increased Cmax and shortened Tmax. 5. Although sorbitol did not reduce the adsorptive efficacy of charcoal, its use alone may be deleterious in poisoning with sustained-release theophylline products.

Adult↗

The effect of iodine on lymphocytic thyroiditis in the thymectomized buffalo rat.

Excess iodine has been associated with an increased incidence of lymphocytic thyroiditis (LT) in the BB/W rat, obese strain chicken, and hamster. The spontaneous incidence of LT in the Buffalo (Buf) rat is increased by neonatal thymectomy. In the present study, the effect of combined thymectomy and excess iodine ingestion on the incidence of LT in Buf rats has been examined. Buf rats were thymectomized at 1 day of age and randomized at 4 weeks of age to receive either standard rat chow with tap water (controls), or standard rat chow with 0.05% iodine in the drinking water (iodine group) for 12 weeks. The serum was assayed for TSH, antithyroglobulin antibodies, and iodine. The thyroids were fixed in Bouin's solution and stained with hematoxylin and eosin, and the presence of thyroiditis was determined. Iodine increased the incidence of LT from 31% in the control group to 73% in the iodine-treated group (P less than 0.05). Serum TSH concentrations and levels of thyroglobulin antibodies were significantly higher in the iodine-treated rats, primarily due to the increased incidence of LT and subsequent iodine-induced hypothyroidism. These data suggest that iodine enhances the effect of neonatal thymectomy on LT in Buf rats and support the concept that iodine may play an important role in the expression of LT in predisposed animals.

Animals↗

Recombinant vaccinia virus expressing the herpes simplex virus type 1 glycoprotein C protects mice against herpes simplex virus challenge.

The gene encoding the herpes simplex virus type 1 (HSV-1) glycoprotein C (gC) was isolated and cloned into a vaccinia virus insertion vector, and the resulting vaccinia-gC vector was used to construct a recombinant vaccinia virus that expressed gC (VVgC5). Infection of cells with VVgC5 resulted in cell surface expression of authentic HSV-1 gC. HSV-1 gC-specific neutralizing antibodies were produced in VVgC5-immunized mice, and lymphocytes exhibited an HSV-1-specific proliferation response in vitro following infection. More importantly, VVgC5-immunized mice were resistant to subsequent lethal HSV-1 challenge.

Animals↗

Infundibular metastasis and panhypopituitarism.

A patient with no known history of primary neoplasia presented with panhypopituitarism secondary to metastasis. Complete anterior pituitary failure was documented by pituitary reserve testing. However, at autopsy there was extensive carcinomatous invasion of the hypothalamus and infundibulum but no adenohypophyseal involvement. The possibility of metastatic disease should be considered in patients presenting with panhypopituitarism. The literature covering this topic is reviewed.

Carcinoma, Small Cell↗

Effect of L-thyroxine administration on the incidence of iodine induced and spontaneous lymphocytic thyroiditis in the BB/Wor rat.

Chronic L-thyroxine administration (6 micrograms/100g BW, ip, daily) for 2 or 3 months suppressed serum TSH concentrations and decreased both the incidence of spontaneous lymphocytic thyroiditis (LT) and the serum levels of anti-thyroglobulin (anti-Tg) antibodies in the diabetes prone BB/Wor rat. This suggests that TSH may play a role in the occurrence of LT in this rat model. In contrast to these observations, L-thyroxine administration did not affect the markedly increased incidence of LT or the elevated serum anti-Tg antibodies in iodine supplemented BB/Wor rats, suggesting that TSH stimulation is not necessary for the development of iodine induced LT in this rat model. Other factors, such as the increased antigenicity of highly iodinated Tg, may be more important.

Animals↗

The effect of charcoal on mefenamic acid elimination.

Mefenamic acid suppository 500 mg was administered by rectum to eight healthy adult volunteers followed by either activated charcoal 5 g orally at hourly intervals for 7 h or an equal volume of water on two separate occasions 7 days apart. Administration of charcoal did not significantly affect the pharmacokinetic variables of mefenamic acid. Thus the beneficial effects of charcoal in the treatment of mefenamic acid overdose are largely due to interference with absorption, rather than enhancement of elimination of the drug.

Adult↗

Iodine-induced thyroiditis and hypothyroidism in the hemithyroidectomized BB/W rat.

We have recently reported that iodine administration (0.05% iodine in drinking water) to weanling, diabetes mellitus- and lymphocytic thyroiditis (LT)-prone Biobreeding Worcester (BB/W) rats strikingly increases the incidence of LT without occurrence of iodine-induced hypothyroidism, which frequently results when excess iodine is administered to euthyroid patients with Hashimoto's thyroiditis. Since hypothyroidism did not occur in the iodine-treated BB/W rats, hemithyroidectomy was carried out in 30-day-old BB/W rats to increase thyroid mass and functional reserve. Iodine administration for 60 days markedly increased antithyroglobulin antibodies (0.40 +/- 0.08 vs. 0.15 +/- 0.06 OD; P less than 0.02), the incidence of LT (68% vs. 13%; P less than 0.001), and thyroid weight of the residual lobe (10.5 +/- 0.7 vs. 6.3 +/- 0.3 mg/100 g BW; P less than 0.001) and induced hypothyroidism (T4, 2.5 +/- 0.2 vs. 3.0 micrograms/dL; P less than 0.05; T3, 25.1 +/- 1.9 vs. 37.5 ng/dL; P less than 0.001; TSH, 252 +/- 49 vs. 61 +/- 14 microU/mL; P less than 0.02). Hypothyroidism in the iodine-treated rats occurred primarily in those with LT. Similar studies were carried out in the non-diabetes mellitus-, non-LT-prone, genetically equivalent BB/W rats (W-line), the parent strain Wistar-Furth rats, and Sprague-Dawley rats. Iodine administration did not induce LT or antithyroglobulin antibodies in these three strains and did not affect thyroid function in Wistar-Furth and Sprague-Dawley rats. However, in the W-line rats, iodine excess did induce thyroid enlargement in the residual lobe (8.4 +/- 0.2 vs. 6.4 +/- 0.2 mg/100 g BW; P less than 0.001), a decrease in serum T3 (71.5 +/- 2.9 vs. 86.0 +/- 2.5 ng/dL; P less than 0.001), and an increase in serum TSH (344 +/- 65 vs. 69 +/- 6.0 microU/mL; P less than 0.001). It is evident, therefore, that hemithyroidectomy in BB/W rats sufficiently reduces functioning thyroid tissue, resulting in iodine-induced LT and hypothyroidism, similar to iodine-induced hypothyroidism in euthyroid patients with Hashimoto's thyroiditis. It is unclear, however, why iodine administration also induced hypothyroidism in hemithyroidectomized, genetically similar, W-line rats in the absence of LT. This observation suggests that iodine-induced hypothyroidism in rats may be genetically determined.

Animals↗

Effect of iodine intake and methimazole on lymphocytic thyroiditis in the BB/W rat.

Spontaneous LT and elevated serum anti-Tg occur in the diabetes prone BB/W rat, but thyroid function is essentially normal in the rats with LT. Prolonged low dose MMI decreases the incidence of LT in BB/W rats. The administration of excess iodine beginning at 30 days of age markedly accelerates the occurrence of LT and anti-Tg at 90 days of age. Low iodine intake decreases the incidence of LT. Excess iodine intake did not induce LT in W-line, Wistar-Furth, and Sprague-Dawley rats. This suggests that iodine induced LT occurs only in genetically susceptible rats. Despite the increased incidence of LT during iodine administration, thyroid function remains essentially normal. This is in contrast to the frequent induction of hypothyroidism following iodine administration to euthyroid patients with Hashimoto's thyroiditis. In order to decrease thyroid reserve, rats were hemi-TX at 30 days of age. The administration of iodine markedly increased the incidence of LT and serum anti-Tg, increased the weight of the remaining lobe, and induced hypothyroidism as determined by significantly lower serum T4 and T3 concentrations and elevated serum TSH concentrations. Excess iodine administration to hemi-TX W-line rats (genetically equivalent, non-diabetes, non-LT prone BB/W rats) did not induce LT but did induce hypothyroidism, suggesting that BB/W and W-line rats are susceptible to iodine induced hypothyroidism, perhaps unrelated to the induction of LT. Excess iodine did not induce LT or affect thyroid function in hemi-TX Wistar-Furth and Sprague-Dawley rats.

Animals↗

Splenic regulation of the murine pulmonary lymph node response.

Exposure to intratracheal immunization and aerosolization with soluble antigen plus murmayl-dipeptide (MDP) induces the development of plaque-forming cells in the pulmonary draining lymph nodes of two of three inbred mouse strains. Splenectomy before immunization led to a heightened plaque-forming cell response in the two responder mouse strains. Adoptive transfer of spleen cells from one strain exposed to sperm whale myoglobin via the respiratory tract revealed the presence of antigen-specific suppressor cells. These observations suggest that the spleen may play a role in the down-regulation of an immune response elicited in the pulmonary draining lymph nodes by exposure of the respiratory tract to soluble antigens plus MDP.

Animals↗

Human cognitive function following binedaline (50 mg and 100 mg) and imipramine (75 mg): results with a new battery on tests.

The effects of two single oral doses of binedaline (50 and 100 mg), imipramine (75 mg) and placebo were compared on a range of psychological tasks (logical reasoning, the Stroop test, and five-choice serial reaction) in healthy young volunteers. The tasks, together with a mood adjective check-list, were completed prior to drug administration and 1, 2, 4 and 8 h post-dose. Binedaline had no significant effect on any of the task parameters. Imipramine impaired performance on all but the Stroop test at 2 h after drug administration. At 1, 2 and 4 h, ratings on the "deactivation" dimension of the mood adjective check-list were significantly higher following imipramine when compared to placebo. The results are discussed in terms of some general considerations about the selection and scoring of tasks to be used in the screening of drugs.

Adult↗

The effect of methimazole on the development of spontaneous lymphocytic thyroiditis in the diabetes-prone BB/W rat.

UNLABELLED: Methimazole (MMI) administration decreases the incidence and intensity of experimentally induced lymphocytic thyroiditis (LT) in the female August rat and male A/J mouse. Spontaneous LT frequently occurs in the insulin-dependent type-I diabetic (DM) BB/W rat. Experiments were carried out to determine whether MMI administration to BB/W rats from 30 to 120 days of age would affect the incidence and intensity of spontaneous LT and the incidence of spontaneous DM. A total of 870 ng MMI/gm BW or saline (C) were administered ip daily to 77 BB/W rats beginning at age 30 days. Rats were killed at 120 days, blood obtained for measurement of serum T4, TSH, and anti-Tg Ab (ELISA), and thyroids removed for histology. MMI administration was associated with a decrease in the incidence of LT (31% vs. 55%; p less than 0.05) but no difference in the severity of the LT. Serum T4 was similar in the MMI and C groups, but serum TSH was slightly but significantly higher in MMI treated rats [43 +/- 6 (mean +/- SE) microU/ml vs. 30 +/- 2.5; p less than 0.05]. Serum anti-Tg Ab levels increased with age but MMI administration did not affect this rise. There was no significant difference in the incidence of insulin-dependent DM between the MMI and C rats (MMI, 56%; C, 74%). CONCLUSION: MMI administration to the genetically predisposed insulin-dependent diabetes and LT prone BB/W rat during the age when LT spontaneously occurs reduced the incidence of LT.

Animals↗