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Biomedical subjects

J F Williams

Publications and source records attributed to J F Williams.

At least 271 records · Page 15Linked to original sources

Adenovirus transcription. IV. Synthesis of viral-specific RNA in human cells infected with temperature-sensitive mutants of adenovirus 5.

Cytoplasmic RNA sequences produced in HeLa cells infected with the adeno-virus 5 temperature-sensitive mutants ts1, ts2, ts9, ts17, ts18, ts19, ts20, ts22, ts49, ts36, and ts125 were characterized by hybridization to DNA probes generated by strand separation of restriction endonuclease fragments of adenovirus 5 DNA. Two ""early'' mutants defective in DNA synthesis, ts125 and ts36, fail to make wild-type levels of all previously reported classes of late RNA at the nonpermissive temperature. At 40.5 degrees C, both ts125 and ts36 synthesize a wild-type complement of early cytoplasmic RNA 16 h after infection. Under these conditions, no ""late'' cytoplasmic RNA sequences were observed. Similarly, nuclear RNA present in these cells resembled early cytoplasmic RNA rather than late nuclear RNA. All the late adenovirus 5 temperature-sensitive mutants synthesized normal wild-type levels of late cytoplasmic RNA at the nonpermissive temperature, except ts2, which appears to overproduce certain cytoplasmic species.

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Effect of exercise conditioning on the intrinsic contractile state of cat myocardium.

Fourteen adult cats were exercised on a motor-driven treadmill 5 days each week for 6 weeks to determine the effect of exercise conditioning on the intrinsic contractile state of the myocardium. The exercise program was sufficient to produce a cardiovascular training effect manifested by slower exercising heart rates and resting heart rates after atropine by the end of the 6th week. The mechanical function of the isolated right ventricular papillary muscle from exercised cats was compared with that of 17 sedentary adult cats. There were no significant differences between exercised and control cats in in heart weight-body weight ratios, resting and active lenght - tension relations, maximal rate of isometric force development at the peak of the length-tension curve (Lmax), time to peak force at Lmax, maximal force development with paired stimulation and norepinephrine, or force-velocity relations. These results indicate that the intrinsic state of feline myocardium is unaffected by exercise conditioning.

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Model ecosystem evaluation of the environmental impacts of the veterinary drugs phenothiazine, sulfamethazine, clopidol, and diethylstilbestrol.

Four veterinary drugs of dissimilar chemical structures were evaluated for environmental stability and penchant for bioaccumulation. The techniques used were (1) a model aquatic ecosystem (3 days) and (2) a model feedlot ecosystem (33 days) in which the drugs were introduced via the excreta of chicks or mice. The model feedlot ecosystem was supported by metabolism cage studies to determine the amount and the form of the drug excreted by the chicks or mice. Considerable quantities of all the drugs were excreted intact or as environmentally short-lived conjugates. Diethylstilbestrol (DES) and Clopidol were the most persistent molecules, but only DES bioaccumulated to any appreciable degree. Phenothiazine was very biodegradable; sulfamethazine was relatively biodegradable and only accumulated in the organisms to very low levels. Data from the aquatic model ecosystem demonstrated a good correlation between the partition coefficients of the drugs and their accumulation in the fish.

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Immunological response to experimental echnococcosis in Meriones unguiculatus.

Varying doses of protoscolices of Echinococcus granulosus were injected intraperitoneally into Mongolian jirds, Swiss mice, and golden hamsters. After 4 months the animals were killed and the numbers of developing cysts counted. Jirds were by far the most susceptible hosts. Doses of 500 protoscolices produced 100% infection rates in both weanlings and adults. Comparable infection rates in weanling mice required inocula of 5,000 protoscolices, but even at this dose hamsters were refractory to infection. Three of 5 jirds developed pulmonary cysts after intravenous administration of 500 protoscolices. Serologic responses in infected jirds were followed using the indirect hemagglutination tests and a purified fraction of hydatid cyst fluid (HCF) as antigen. Titers reached a plateau after 15 weeks and were maintained for several months. Much brisker serologic responses occurred in animals sensitized with the antigenic fraction in various adjuvant vehicles. At no time during infection did jirds show any evidence of immediate hypersensitivity to HCF in direct skin tests, passive cutaneous anaphylactic tests, or after intravenous challenge with antigen. After artificial immunization with hapten-conjugated antigens or HCF, jirds underwent a fatal shock following intravenous challenge with antigen. HCF provoked the appearance of circulating antibodies which were capable of sensitizing normal recipients for passive systemic anaphylaxis after a latent period of 72 hr. It is concluded that the failure of the infected jird to develop immediate hypersensitivity responses to E. granulosus represents a marked deviation from the parrern of the immune response in echinococcosis in man and domestic animals and must be considered in the future use of this animal in experimental studies on the host-parasite relationship.

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The eosinophilic response of the rat to infection with Taenia taeniaeformis.

Rats were dosed with eggs of Taenia taeniaeformis and hematologic parameters were measured throughout the course of primary infection. There was no evidence of anemia but differential leukocyte counts revealed distinct and reproducible patterns of white blood cell changes. A lymphocytosis developed at the end of the 1st and 5th weeks postinfection (p.i.). Neutrophil counts peaked 8 days p.i., although at that time there was no marked neutrophilic infiltration of the tissues. Eosinophil counts began to rise during the 2nd week p.i., and reached a peak during the 3rd week, followed by a decline and then another peak during the 5th week p.i. Eosinophilic infiltration of the tissues was remarkable during the period of peripheral eosinophilia. A wide zone of eosinophils surrounded the developing larvae at 22 days p.i. and persisted in some cases for a further 2 weeks. Eosinophils remained in lesser numbers in the connective tissue capsule throughout the infection, often in association with plasma cells. After oral challenge with 1,000 eggs infected rats showed brisk secondary eosinophilic responses 3 to 7 days later but other hematologic parameters were unaffected. Average peripheral eosinophil counts at 3 and 4 days post-challenge were significantly higher than those in unchallenged controls (P less than 0.05 and P less than 0.01, respectively). There was no detectable increase in eosinophilic infiltration of small intestinal tissues in challenged rats. These results are discussed in relation to current understanding of the mechanisms of eosinophil chemotaxis in vitro and the possible causes of local eosinophil accumulation in parasitic infections in vivo.

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Antibody-mediated secondary eosinophilic response to Taenia taeniaeformis in the rat.

Normal rats were given intravenous doses of either immune serum or immunoglobulin fractions 24 hr before oral challenge with 1,000 eggs of Taenia taeniaeformis. Total eosinophil counts per mm3 were performed for 3 days prior to and 6 days after challenge. Sensitized rats usually showed sharp peaks of eosinophilia 2 to 6 days after this dose. The pattern of the eosinophilic response was similar to that which occurs after challenge of immune infected rats. The differences in peripheral eosinophil levels in passively immunized and normal rats were statistically significant. Immunoglobulin fractions containing protective IgG2alpha were most effective, but a fraction containing reaginic antibody activity also sensitized rats to give secondary eosinophilic responses. The findings are discussed in relation to the probable contribution of antigen-antibody reactions to the production of secondary eosinophilic responses in experimental cysticercosis.

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Learning disability: a multifaceted health threat an optometric question.

A conceptual model for the natural history of learning disabilities as a health threat will be presented. The model illustrates the multitude of individual and environmental factors influencing the subsequent physical and mental well-being of disabled learners as well as the professional interaction and interdisciplinary cooperation needed to limit if not prevent the societal impact of learning disabilities.

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The localisation of sorbitol pathway activity in the rat renal cortex and its relationship to the pathogenesis of the renal complications of diabetes mellitus.

A series of in vivo and in vitro investigations was performed to examine the localisation of sorbitol pathway activity in the rat renal cortex and to investigate the possible relation that the acculumation of sorbitol pathway intermediates in renal cortical tissue may have to the pathogenesis of renal complications in diabetes mellitus. Neither of the sorbitol pathway intermediates, sorbitol or fructose, were detected either in intact glomeruli which had been isolated from rats rendered chronically diabetic with streptozotocin, or in metabolically active glomeruli which had been incubated in vitro in high glucose media. Such data agreed with previously published observations that the enzyme aldose reductase is not present in renal glomeruli, and suggested that changes in sorbitol pathway activity cannot be directly related to the pathogenesis of diabetic glomerulosclerosis. Sorbitol was detected in low concentrations (3.1 mu-mol/g protein) in cortical tubules which had been isolated from the renal cortex of rats rendered chronically diabetic with streptozotocin. This concentration of sorbitol was higher than that in the intact renal cortex of the diabetic animal (0.3 mu-mol/g protein) or in the cortical tubules of non-diabetic animals (0.5 mu-mol/g protein). It is apparent that the renal cortical tubule is a major site of sorbitol pathway activity in the renal cortex. However, there is presently no obvious causal relationship between the accumulation of such relatively low concentrations of sorbitol in the renal cortical tubule and the pathogenesis of glomerulosclerosis or cortical tubular lesions in diabetes.

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Osmotic effects of sorbitol accumulation in monkey kidney epithelial cell cultures.

It has been observed that primary monolayer cell cultures derived from monkey kidney cortex behave in a similar manner to the mammalian lens in that they accumulate high concentrations of sorbitol when they are incubated in medium containing a high glucose concentration (33 mM). An investigation was undertaken to determine whether the accumulation of sorbitol by these cultures results in cellular damage by an osmotic mechanism similar to that which has been proposed to occur in the lens. Phase-contrast microscopy and histochemical investigations revealed that no changes in the cell size, cell growth rate, or cell staining properties occurred as a result of exposure of the cell cultures to a glucose concentration of 33mM for up to 4 days. The cell protein and myo-inositol concentrations and fatty acid composition were also unaffected, as was the incorporation of radioactivity from [U-14C]leucine into cell protein. The rate of 86Rb influx of the cell cultures was decreased and the rate of 86Rb efflux was increased by incubation in medium containing a glucose concentration of 33 mM. Frome these observations it was concluded that the accumulation of sorbitol by monkey kidney epithelial cell cultures did not exert a pathabolic influence upon their growth and metabolism, and that these cells, unlike the lens, have the capacity to compensate adequately for changes in transmembrane osmotic gradients induced by sorbitol accumulation.

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The effect of chronic digitoxin administration on the contractile state of normal and nonfailing hypertrophied myocardium.

To determine the effect of prolonged digitoxin administration on contractile function of nonfailing myocardium, right ventricular papillary muscle mechanics were examined after 6 or 24 wk of glycoside administration to control and pulmonary artery banded cats. Resting length-tension relations were not affected by digitoxin; however, isometrically developed force and the maximal rate of force development at the peak of the length-tension curve were increased in all treated groups. In untreated animals, banding resulted in a 28% incidence of deaths from heart failure. 6 wk after constriction, contractile function was depressed whereas normal function was observed 24 wk after banding. Digitoxin significantly reduced mortality from heart failure and enhanced the recovery of contractile function; contractile function in the 6 wk banded treated group approached that of untreated control and 24-wk banded groups. The long-term effects of digitoxin on contractile function were not importantly related to the temporal association between banding and institution of glycoside administration. Development of myocardial hypertrophy was comparable in treated and untreated banded groups.These results demonstrate that a significant positive inotropic effect persists in both normal and nonfailing hypertrophied myocardium during chronic digitoxin administration.

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