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Biomedical subjects

C Ludlow

Publications and source records attributed to C Ludlow.

14 recordsLinked to original sources
PubMed2001

Thymidine incorporation is highly predictive of colony formation and can be used for high-throughput screening.

The primary goal of anticancer chemotherapy is to kill cancer cells. Therefore, it is of critical importance that any assay that is used to determine the toxicity of a potential anticancer drug accurately measures viability. While colony formation is widely regarded as the most accurate measure of viability following drug treatment, it is laborious, time consuming, and difficult to carry out with non-adherent cells. For these reasons, it is not suitable for moderate- to high-throughput screening applications. We sought to identify a convenient and reliable assay that would accurately reproduce colony formation results and be amenable to high-throughput applications. Here, we describe a modification of the 3H-thymidine incorporation assay that meets these criteria. The assay can be carried out in 96-well plates with minimal handling of reagents and media. It can be performed with non-adherent and adherent cell lines. Most importantly, LC50 values obtained with this assay show excellent agreement with colony formation results. Taken together, these advantages make the modified 3H-thymidine incorporation assay well suited for high-throughput viability assays in anticancer drug discovery and development.

Animals↗
PubMed2000

Differential toxicities of anticancer agents among DNA repair and checkpoint mutants of Saccharomyces cerevisiae.

Most cytotoxic anticancer agents damage DNA directly, interfere with DNA metabolism or chromosome segregation, and are particularly toxic in dividing cells. Although a considerable amount of information on the mechanisms of action of these agents is available, the molecular bases for selective tumor cell killing by chemotherapy are largely unknown. Many genetic alterations found in sporadic and hereditary cancers affect functions in DNA repair and cell cycle control and result in sensitivity to DNA damaging agents. We have therefore set out to determine the effects of these cancer mutations on sensitivity or resistance to various chemotherapeutic agents. Because most of the affected genes are well conserved among eukaryotes, we have carried out a comprehensive analysis of a panel of isogenic yeast strains, each defective in a particular DNA repair or cell cycle checkpoint function, for sensitivity to the Food and Drug Administration-approved cytotoxic anticancer agents. Widely different toxicity profiles were observed for 23 agents and X-rays, indicating that the type of DNA repair and cell cycle checkpoint mutations in individual tumors could strongly influence the outcome of a particular chemotherapeutic regimen.

Antimetabolites, Antineoplastic↗
PubMed1999

Experimental approaches to vocal fold alteration: introduction to the minithyrotomy.

Treatment of challenging laryngeal disorders, such as lamina propria loss or neuromuscular dysfunction, may require novel approaches and techniques. This paper discusses an evolution of experimental techniques for treatment of lamina propria loss and use of the minithyrotomy. These techniques have been used for surgical access for lamina propria substitution, as well as placement of stimulating electrodes. The minithyrotomy is tolerated well by patients, provides access for microscopic instruments with the surgeon's hand close to the tissue of interest, avoids intralaryngeal mucosal incisions, and lines up the direction of dissection in an anterior-to-posterior orientation. This orientation is favorable for particular situations herein discussed. We present anatomic and physiologic concepts relevant to the surgical treatment of lamina propria dysfunction, as well as presenting our clinical experience. This paper is not intended to state how these difficult problems should be handled, but rather, to present our experience in techniques that may prove useful through further development.

Adipose Tissue↗
PubMed1996

Functional analysis of Drosophila and mammalian cut proteins in files.

The cut locus acts as a bimodal switch controlling cell fate in the peripheral nervous system of Drosophila and is also required for the development of the wing margin. It encodes a protein, Cut, that contains an atypical homeodomain and three copies of a new motif which can bind DNA in vitro. The human protein CDP and the murine protein Cux have recently been isolated as DNA-binding activities and they are structurally related to Cut. We show that ectopic expression of Cut, CDP, or Cux similarly affects embryonic sensory organ development and can rescue a wing scalloping mutant phenotype associated with loss of cut expression along the prospective wing margins. This suggests that the function of Cut is evolutionarily conserved.

Animals↗
PubMed1988

Intellectual function following penetrating head injury in Vietnam veterans.

The extent to which intellectual processes are preserved as a function of preinjury 'intelligence' and of size and location of the brain lesions was evaluated in Vietnam war veterans who survived penetrating missile wounds. With regard to an overall postinjury intelligence test score, preinjury intelligence was most predictive, size of lesion was next most predictive and lesion location was least important. For subtest scores from the same intelligence test, lesion location assumed much greater predictive value. Specifically, left temporal and occipital lesions impaired performance on subtests assessing vocabulary and object-function matching ability.

Adult↗
PubMed1986

Consciousness and amnesia after penetrating head injury: neurology and anatomy.

Among 342 men who survived severe penetrating brain wounds, only 15% had prolonged unconsciousness and 53% had no or momentary unconsciousness after injury, emphasizing the focal nature of these wounds. The left (or language-dominant) hemisphere was dominant for the "wakefulness" component of consciousness. The areas most associated with unconsciousness included the posterior limb of the left internal capsule, left basal forebrain, midbrain, and hypothalamus. Left dominance was not seen for posttraumatic amnesia after elimination of the wakefulness variable, suggesting that wakefulness may be linked to the role of the left hemisphere in verbal memory.

Amnesia↗
PubMed1986

Penetrating war injuries of the basal forebrain: neurology and cognition.

We compared the neurologic and cognitive performance of 15 young veterans who suffered unilateral penetrating missile wounds to the basal forebrain 15 years ago in the Vietnam War with uninjured controls and patients with lesions elsewhere in the brain. The subjects performed worse on tests of episodic memory, reasoning, and arithmetic and had more prolonged unconsciousness after injury; but their performance usually compared favorably with that of uninjured controls on tests of intelligence, attention, and language and was not consistent with that of a demented patient. The data suggest that the basal forebrain is functionally related to the reticular formation and to the basal forebrain is functionally related to the reticular formation and to the limbic-hippocampal memory system.

Basal Ganglia↗
PubMed1985

Isolated impairment of memory following a penetrating lesion of the fornix cerebri.

Persistent memory problems were reported by a 39-year-old man who suffered a penetrating brain wound while serving in Vietnam 15 years earlier. Neuropsychological testing indicated an unusually isolated memory impairment. Computed tomography revealed transection of the columns of the fornix cerebri with no temporal-lobe involvement and minimal thalamic damage. We suggest that the fornix cerebri has a role in the maintenance of information accessibility to both encoding and recall during post-working memory processing and in the organization of verbal information during encoding and/or retrieval for declarative (recall) purposes. These processes are not essential for verbal recognition but can result in decrements on specific laboratory tasks and in social adjustment.

Adult↗
PubMed1981

Behavioral and cognitive effects of caffeine in boys and adult males.

The behavioral and cognitive effects of single doses of caffeine (3 and 10 mg/kg) were studied using a double blind placebo-controlled crossover design. Subjects were 19 prepubertal boys and 20 college age men. In general, children tended to show more objective effects of caffeine than did adults, with increased motor activity, increased speech rate, and decreased reaction time. Adults generally reported side effects following caffeine while children did not, and side effects were more prominent for adults with low habitual caffeine intake. Autonomic measures of arousal were similarly affected for both age groups. Caffeine had some effects that differed from those of amphetamine, indicating distinctive actions of the two stimulants.

Adult↗
PubMed1981

Childhood obsessive-compulsive disorder.

The authors collected clinical diagnostic, neurophysiological, electrophysiological, and biochemical data on 9 adolescents who had primary obsessive-compulsive disorder. The results indicate considerable descriptive validity of the syndrome in childhood and its independence from obsessional traits; however, all of the children had a history of major depressive disorder, and their sleep EEG measures resembled those of young adults with primary depressive disorder. The patients' families did not have a more consistent pattern of anxiety disorder or any other psychiatric disorder than do families of adult obsessive patients. Psycholinguistic test results showed a lack of normal laterality, which has been reported for other psychiatric illness.

Adolescent↗
PubMed1980

Dextroamphetamine. Its cognitive and behavioral effects in normal and hyperactive boys and normal men.

The effects of a single oral dose of dextroamphetamine sulfate on motor activity, vigilance, learning, and mood were compared for normal and hyperactive prepubertal boys and normal college-aged men using a double-blind crossover design. Both groups of boys and men showed decreased motor activity increased vigilance, and improvement on a learning task after taking the stimulant drug. The men reported euphoria, while the boys reported only feeling "tired# or "different# after taking the stimulant. It is not clear whether this difference in effect on mood between adults and children is due to differing experience with drugs, ability to report affect, or a true pharmacologic age-related effect. While there were some quantitative differences in drug effects on motor activity and vigilance between these different groups, stimulants appear to act similarly on normal and hyperactive children and adults.

Adolescent↗
PubMed1978

Dextroamphetamine: cognitive and behavioral effects in normal prepubertal boys.

The behavioral, cognitive, and electrophysiological effect of a single dose of dextroamphetamine (0.5 milligram per kilogram of body weight) or placebo was examined in 14 normal prepubertal boys (mean age, 10 years 11 months) in a double-blind study. When amphetamine was given, the group showed a marked decrease in motor activity and reaction time and improved performance on cognitive tests. The similarity of the response observed in normal children to that reported in children with "hyperactivity" or minimal brain dysfunction casts doubt on pathophysiological models of minimal brain dysfunction which assume that children with this syndrome have a clinically specific or "paradoxical" response to stimulants.

Attention Deficit Disorder with Hyperactivity↗