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Biomedical subjects

D Clark

Publications and source records attributed to D Clark.

At least 307 records · Page 17Linked to original sources

The effect of the enantiomers of 3-PPP on conditioned avoidance responding in the rat.

The effects of the enantiomers of 3-PPP on the maintenance of conditioned avoidance responding (CAR) were studied. The weak classical dopamine (DA) agonist (+)-3-PPP failed to interfere with CAR at any dose tested (0.8-13.6 mg/kg). Low doses of the drug produced sedation, while high doses produced behavioural stimulation. (-)-3-PPP, which acts as an antagonist on postsynaptic and as an agonist on autoreceptor DA sites, reduced avoidance with no effect on escape behaviour (6.8-13.6 mg/kg). However, this reduction of CAR occurred at doses much higher than those previously demonstrated to inhibit locomotor activity. This profile is discussed in relation to the behavioural effects of classical postsynaptic DA receptor antagonists.

Animals↗

A glycogen storage disease in rats. Morphological and biochemical investigations.

Liver and heart from a substrain of the NZR/Gd rat in which there is an inherited deficiency of liver phosphorylase b kinase was examined by light and electron microscopy and compared to material from a related, but normal substrain. Hepatic tissue differed markedly from that of control animals. Hepatocytes contained more than twice as much free glycogen and visible lipid. Glycogen particles had an abnormal appearance and some glycogen was sequestered within large, membrane-bound vesicles. Hepatocyte lysosomes were increased by a third and mean cell volume by more than half. Lobular architecture was distorted by the presence of enlarged, irregularly-shaped hepatocytes. Free glycogen was present in the space of Disse and sinusoids and within lysosomes in Kupffer cells. There were increased amounts of collagen in the space of Disse. The changes resemble those described in human glycogen storage disease IXa. A study of hepatic tissue from fasted rats showed that affected animals have an impaired ability to mobilise their liver glycogen stores. An increase in visible lipid also occurred in affected, fasted animals. Cardiac tissue appeared to be normal.

Animals↗

Ambulation in severe arthrogryposis.

Functional ambulation occurred in 22 of 36 severely affected arthrogrypotic patients. Functional ambulation in these patients required hip motion to within 30 degrees of full extension and knee motion to within 20 degrees of full extension. Ambulation also required hip extensor strength of good (grade 4), quadriceps strength of fair (grade 3), or crutchable upper extremities and orthotic substitutes. Foot and spine deformities also interfered with ambulatory ability.

Adolescent↗

Role for fadR in unsaturated fatty acid biosynthesis in Escherichia coli.

Escherichia coli K-12 mutants constitutive for the synthesis of the enzymes of fatty acid degradation (fad) synthesize significantly less unsaturated fatty acid (UFA) than do wild-type (fadR+) strains. The constitutive fadR mutants synthesize less UFA than do fadR+) strains both in vivo and in vitro. The inability of fadR strains to synthesize UFAs at rates comparable to those of fadR+ strains is phenotypically asymptomatic unless the fadR strain also carries a lesion in fabA, the structural gene for beta-hydroxydecanoyl-thioester dehydrase. Unlike fadR+ fabA(Ts) mutants, fadR fabA(Ts) strains synthesize insufficient UFA to support their growth even at low temperatures and, therefore, must be supplemented with UFA at both low and high temperatures. The low levels of UFA in fadR strains are not due to the constitutive level of fatty acid-degrading enzymes in these strains. These results suggest that a functional fadR gene is required for the maximal expression of UFA biosynthesis in E. coli.

Enzymes↗

Pichinde virus-specific cell-associated suppression of primary footpad swelling in an inbred strain of Syrian hamsters.

Pichinde virus causes a lethal disease after i.p. inoculation of adult MHA hamsters; other strains of Syrian hamsters are resistant to this lethal infection. During studies of cell-mediated immune responses to Pichinde virus, it was noted that MHA hamsters survived infection when the virus was given in the footpad. However, unlike the resistant LSH and LVG strains of hamsters, the MHA hamsters did not manifest a footpad swelling response. Failure of the MHA hamster to respond to a footpad inoculation of Pichinde virus was shown to be virus-specific and appeared to be mediated by a cell-associated suppressor mechanism.

Animals↗

Jules Tinel and Tinel's sign.

This important tingling sign of nerve healing was described by Jules Tinel, a distinguished French neurologist, in 1915. A description of a contemporaneous report of this sign by Paul Hoffman and a short biography of Tinel are presented.

History, 20th Century↗

The search for selective dopaminergic autoreceptor agonists.

In the course of a search for new selective dopamine (DA) autoreceptor agonists the DA analogue 3-(3-hydroxyphenyl)-N-n-propylpiperidine, 3-PPP, was resolved into its dextro-(+) and levo-(-) rotatory enantiomers. The compounds were pharmacologically evaluated by means of behavioural and biochemical methods. Surprisingly, both (+)-and (-)-3-PPP show clearcut, but differential, effects on the DA receptors. Thus, (+)-3-PPP is a DA receptor agonist with activity on autoreceptors as well as postsynaptic receptors, whereas (-)-3-PPP similarly activates DA autoreceptors but, in contrast, concomitantly acts as an antagonist on postsynaptic DA receptors. Moreover, the behavioural/biochemical profile seems to indicate a preferential limbic action for the (-)-enantiomer. Such an action could be explained on the basis of different feedback arrangements in the nigrostriatal and mesolimbic DA systems and it is suggested that compounds such as (-)-3-PPP may find future clinical application as "second-generation" antipsychotic agents, lacking in the debilitating motor side effects produced by drugs in current therapeutic use.

Animals↗

Intraoperative irradiation: a pilot study combining external beam photons with "boost" dose intraoperative electrons.

Intraoperative "boost" dose electron beam therapy given in combination with 4500--5000 rad (45--50 Gray) external beam irradiation has been demonstrated as a practical therapeutic modality at the MGH. This procedure has been employed thus far in 58 patients; the results in the initial 36 are analyzed in detail in this paper. Thirty-four of the 36 patients had locally advanced lesions--unresectable, recurrent, or residual disease. Results achieved to date are in full agreement with our expectations: high radiation doses have been delivered to the primary intra-abdominal and pelvic tumors, excluding the sensitive structures from irradiation. This has been accomplished by a truly multidisciplinary effort comprising surgery, anesthesiology, OR nursing, administration, engineers, physicists, therapy technologists, and radiation therapists. Although follow-up is not yet sufficient to judge ultimate efficacy, acute and chronic severe morbidity is low and local control is good. There is justified enthusiasm for continuing the procedure.

Female↗

Childhood respiratory illness and the home environment. I. Relations between nitrogen dioxide, temperature and relative humidity.

The relation between the use of gas for cooking, nitrogen dioxide (NO2), temperature and relative humidity was investigated in an urban area of northern England. In a pilot study conducted in a random sample of 40 homes measurements of temperature and relative humidity were not significantly different between homes with a gas cooker and homes with an electric cooker but weekly average levels of NO2 were higher in bedrooms (p less than 0.005) and living rooms (P less than 0.01) of gas homes. In the main study conducted in gas cooking homes only, access was gained to 183 (54.3%) of 337 randomly selected homes. No correlation was found in children's bedrooms between with weekly average level of NO2 (range 4.7 to 160.8 ppb) and weekly average temperature (ranged 7.7 to 22.0 degree C; r = 0.05, p greater than 0.10) or relative humidity (range 37.0 to 98.1%; r = 0.07, p greater than 0.10). Levels of NO2 in the bedroom were positively correlated with those in the living room (range 9.0 to 292.2 ppb; r = 0.39, p less than 0.01). Factors which tended to be associated with high levels of NO2 in the home included gas fires, paraffin heaters and use of the cooker for heating and drying clothes.

Air Pollutants↗

Childhood respiratory illness and the home environment. II. Association between respiratory illness and nitrogen dioxide, temperature and relative humidity.

The relation of respiratory illness to nitrogen dioxide (NO2), temperature and relative humidity in homes with a gas cooker was investigated in five and six year old children living in an urban area of the northern England. NO2 was measured for one week in the child's bedroom and living room of each home, and temperature and relative humidity were measured in the bedroom only. Information on respiratory conditions experienced by the child and characteristics of the home was collected in a self-administered questionnaire completed by the child's mother. Access was gained to 183 homes (54.3% of 337) where only gas was used for cooking. Complete information was obtained for 179 (93.7%) of 191 children who lived in the 183 homes. After allowing for the effects of age, sex, social class, and number of cigarette smokers in the home and temperature or relative humidity, no statistically significant relation was found between the prevalence of having one or more respiratory conditions and weekly average levels of NO2 in the bedroom (range 4.7 to 160.8 ppb) or living room (range 9.0 to 292.2 ppb). However, the prevalence of having one or more respiratory conditions tended to be highest in homes with high levels of NO2 and lowest in homes with low levels, consistent with earlier findings. A significant positive association was found between the prevalence of respiratory conditions and relative humidity (p less than .05). A harmful effect on health from NO2 cannot be totally dismissed but if it exists it is weak and difficult to detect in small samples of children.

Air Pollutants↗

Escherichia coli mutants with a temperature-sensitive alcohol dehydrogenase.

Mutants of Escherichia coli resistant to allyl alcohol were selected. Such mutants were found to lack alcohol dehydrogenase. In addition, mutants with temperature-sensitive alcohol dehydrogenase activity were obtained. These mutations, designated adhE, are all located at the previously described adh regulatory locus. Most adhE mutants were also defective in acetaldehyde dehydrogenase activity.

Alcohol Dehydrogenase↗