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Biomedical subjects

J Lyons

Publications and source records attributed to J Lyons.

At least 37 records · Page 2Linked to original sources

Optimizing the use of vision in manual aiming: the role of practice.

The purpose of this study was to determine how subjects learn to adjust the characteristics of their manual aiming movements in order to make optimal use of the visual information and reduce movement error. Subjects practised aiming (120 trials) with visual information available for either 400 msec or 600 msec. Following acquisition, they were transferred to conditions in which visual information was available for either more or less time. Over acquisition, subjects appeared to reduce target-aiming error by moving to the target area more quickly in order to make greater use of vision when in the vicinity of the target. With practice, there was also a reduction in the number of modifications in the movement. After transfer, both performance and kinematic data indicated that the time for which visual information was available was a more important predictor of aiming error than the similarity between training and transfer conditions. These findings are not consistent with a strong "specificity of learning" position. They also suggest that, if some sort of general representation or motor programme develops with practice, that representation includes rules or procedures for the utilization of visual feedback to allow for the on-line adjustment of the goal-directed movement.

Adult

Intermittent vision and discrete manual aiming.

This study was designed to assess how the precision requirements of discrete aiming movements affect the utility of brief visual samples provided during execution of movement. Subjects pointed with a hand-held stylus to targets with indices of difficulty of 3, 4, 5, and 6 bits with full vision, no vision, and in conditions in which 20-msec. visual samples were provided every 80, 140, or 200 msec. While intermittent vision required slightly longer movement times for targets with a high index of difficulty, subjects' accuracy was similar to the full-vision situation. Moreover, with intermittent vision, the movement trajectories resembled the full-vision and not the no-vision situation. It would appear that brief visual samples of the movement environment are sufficient for reasonably precise closed-loop control.

Adult

Detection of enteroviral ribonucleic acid in myocardial biopsies from patients with idiopathic dilated cardiomyopathy by polymerase chain reaction.

Infection by enteroviruses, especially by Coxsackie B viruses, has been incriminated in pathogenesis of dilated cardiomyopathy. We developed polymerase chain reaction tests for the detection of enteroviral and Coxsackie B3 genomes, respectively, in myocardial biopsies obtained from a homogeneous group of 19 patients with idiopathic dilated cardiomyopathy. To determine unambiguously the incidence of enteroviruses and Coxsackie B3 viruses in these patients, we used two primer pairs, one common to all enteroviruses and the other specific for Coxsackie B3 viruses. In six patients of the dilated cardiomyopathy group, enteroviral ribonucleic acid (RNA) could be detected; only one was subspecified as Coxsackie B3 RNA. In contrast, no enteroviral RNA could be detected in a contrast group of 21 patients with other cardiac disorders. These results suggest that enteroviruses other than Coxsackie B3 are causally linked to the pathogenesis of dilated cardiomyopathy.

Biopsy

The polymerase chain reaction and cancer diagnostics.

In this review, I describe the polymerase chain reaction (PCR) and its application to cancer diagnostics. I present recent improvements to PCR methodology, and describe some state-of-the-art detection methods and approaches used to diagnose various cancer markers, including ras genes, BCR/abl translocations, and G-proteins.

Humans

Early mutation of the neu (erbB-2) gene during ethylnitrosourea-induced oncogenesis in the rat Schwann cell lineage.

The development of malignant tumors of the peripheral nervous system (schwannomas) within a defined intracranial section of the rat trigeminal nerve ("trigeminal box") was used as a model to identify genetic alterations typically associated with the process of cell-lineage-specific oncogenesis induced by exposure to N-ethyl-N-nitrosourea on postnatal day 1. All 47 trigeminal schwannomas (and 12 extracranial neurinomas) investigated carried a T.A----A.T transversion mutation at nucleotide 2012 of the neu (erbB-2) gene sequence encoding the transmembrane domain of pg185neu. This mutation was absent in all 18 tumors in the brain and spinal cord (central nervous system) isolated from the same animals. Identical observations were made in cell lines derived from N-ethyl-N-nitrosourea-induced rat schwannomas vs. brain tumors. By asymmetric PCR and mutant-specific Mnl I restriction fragment length analyses, cells carrying the mutant neu allele became detectable and could be localized within the trigeminal box as early as 7 days after the carcinogen pulse. The proliferation rate of the mutant cells strongly exceeded that of the wild-type cells up to the time of maturation of the trigeminal nerve around postnatal day 30 and thereafter to a lesser extent until the appearance of schwannomas. A specific mutation of the neu gene thus represents a very early, probably the first, step in the malignant conversion of immature rat Schwann cells exposed to N-ethyl-N-nitrosourea in vivo and is diagnostic for a subset of proliferative cells at high risk of progressing toward the expression of fully malignant phenotypes. Loss of heterozygosity for the mutant neu allele is a candidate event for a critical second step in the process.

Alleles

Molecular genetic analysis of DNA obtained from fixed, air dried or paraffin embedded sources.

In the present study methods are described for the analysis of the genomic structure of DNA isolated from tissues that have been stored up to several years as air-dried or stained bone marrow smears, bone marrow biopsies in "Histicon", chromosomal preparations in fixative or as formalin fixed tissues embedded in paraffin. By application of the new techniques clonal B- and T-cell disorders, Philadelphia chromosome translocations and ras oncogene mutations in pancreatic carcinomas could be detected. Thus, these DNA extraction procedures may open new avenues to pathological archives and enable the analysis of samples when fresh material is not available.

Bone Marrow

The relationship of residents' autonomy and use of a teaching hospital's resources.

This 1990 study examines the relationship between the degree of use of patient care resources and the degree of supervision of residents by attending physicians (as perceived by residents) at a large midwestern teaching hospital. Ratings of the degree of clinical autonomy allowed residents by 65 attending physicians--each of whom had a general internal medicine practice with a significant hospital component--were provided by 23 former internal medicine chief residents and 17 internal medicine residents who were in their third year at the time of the study. A regression model was used to test the association between hospital resource use (as shown by total hospital charges to patients and their lengths of stay) and the residents' mean ratings of the degrees of autonomy the attending physicians permitted residents, for 7,169 of these physicians' patients discharged between 1986 and 1989 in 28 diagnosis-related groups. The analysis was controlled for patients' insurance status and chronic disease comorbidities. The patients whose attending physicians were rated as allowing substantial clinical autonomy had significantly lower total charges and lengths of stay (p less than .0001). These results suggest that internal medicine residents have an inherently conservative practice style that values low-intensity workups and rapid discharge of patients.

Aged

Aristolochic acid activates ras genes in rat tumors at deoxyadenosine residues.

Aristolochic acid I (AAI), a nitrophenanthrene derivative, is the major component of the carcinogenic plant extract aristolochic acid, which has been used as a medicine since antiquity. Long term oral administration of AAI to male Wistar rats induces multiple tumors, mainly in the forestomach, ear duct, and small intestine. The presence of activated transforming genes was investigated in various tumors of 18 AAI treated rats, namely in 14 squamous cell carcinomas of the forestomach, 7 squamous cell carcinomas of the ear duct, 8 tumors of the small intestine, 3 tumors of the pancreas, 1 adenocarcinoma of the kidney, 1 lymphoma, and 2 metastases in the lung and the pancreas. By utilizing the tumorigenicity assay and Southern blot analysis, we have detected an activated c-Ha-ras gene in the DNAs of 5 of 5 squamous cell carcinomas of the forestomach. Direct sequencing of amplified material revealed an AT----TA transversion mutation at the second position of codon 61 of the c-Ha-ras gene (CAA to CTA) in all transfectants as well as in the 5 original rat tumors. Enzymatic amplification of ras sequences followed by selective oligonucleotide hybridization detected identical mutations in 93% (13 of 14) of forestomach tumors, in 100% (7 of 7) of ear duct tumors, and in the lung metastasis. Among those tumors tested, we had 4 cases in which the forestomach tumors and the ear duct tumors originated from the same rat, showing the same mutation in both tissues. Moreover, similar mutations were demonstrated at c-Ki-ras codon 61 in 1 of 7 ear duct tumors (CAA to CAT) and in 1 of 8 tumors of the small intestine (CAA to CTA) as well as at c-N-ras 61 (CAA to CTA) in a pancreatic metastasis. Additional transfection experiments of some tumors scoring negative for ras gene mutations in dot blot analyses revealed a CAA to CTA transversion at codon 61 of the c-Ha-ras gene in 1 forestomach tumor as well as at codon 61 of the c-N-ras in 1 hyperplasia of the pancreas and in 1 lymphoma. The apparent selectivity for mutations at adenine residues in AAI induced tumors is consistent with the identification of an N6-deoxyadenosine-AAI adduct formed by reaction of AAI with DNA in vitro, suggesting that carcinogen-deoxyadenosine adducts are the critical lesions in the tumor initiation by aristolochic acid.

Animals

Two G protein oncogenes in human endocrine tumors.

Somatic mutations in a subset of growth hormone (GH)-secreting pituitary tumors convert the gene for the alpha polypeptide chain (alpha s) of Gs into a putative oncogene, termed gsp. These mutations, which activate alpha s by inhibiting its guanosine triphosphatase (GTPase) activity, are found in codons for either of two amino acids, each of which is completely conserved in all known G protein alpha chains. The likelihood that similar mutations would activate other G proteins prompted a survey of human tumors for mutations that replace either of these two amino acids in other G protein alpha chain genes. The first gene so far tested, which encodes the alpha chain of Gi2, showed mutations that replaced arginine-179 with either cysteine or histidine in 3 of 11 tumors of the adrenal cortex and 3 of 10 endocrine tumors of the ovary. The mutant alpha i2 gene is a putative oncogene, referred to as gip2. In addition, gsp mutations were found in 18 of 42 GH-secreting pituitary tumors and in an autonomously functioning thyroid adenoma. These findings suggest that human tumors may harbor oncogenic mutations in various G protein alpha chain genes.

Amino Acid Sequence

Cellular oncogenes in human teratocarcinoma cell lines.

We have analysed, by Northern blots, the expression of 14 cellular oncogenes in nine cell lines established from human teratocarcinomas. All lines expressed considerable amounts of p53, c-Ki-ras2, c-Ha-ras1, c-raf1, N-myc, and c-fos. Low level expression of c-myc was detected in some lines. Southern blot experiments revealed no amplification or rearrangement of the c-Ki-ras2, N-myc or c-fos genes. Using a rapid dot-blot screening procedure, based on a combination of in-vitro amplification of ras-specific sequences and oligonucleotide hybridization, we could detect no activation of Ha-ras or Ki-ras or any unexpressed N-ras sequences secondary to a point mutation at codons 12, 13, or 61.

Blotting, Northern

Expression of Mycobacterium tuberculosis and Mycobacterium leprae proteins by vaccinia virus.

Eight Mycobacterium tuberculosis and M. leprae genes were inserted into the vaccinia virus genome by in vivo recombination. The resulting virus recombinants were shown to express five different M. tuberculosis proteins (71, 65, 35, 19, and 12 kDa) and three M. leprae proteins (65 and 18 kDa and a biotin-binding protein) by Western immunoblot analysis, radioimmunoprecipitation, or black-plaque assay. When injected into BALB/c mice, the recombinants expressing the M. tuberculosis 71-, 65-, or 35-kDa protein and the M. leprae 65-kDa protein or the biotin-binding protein elicited antibodies against the appropriate M. tuberculosis or M. leprae protein. These vaccinia virus recombinants are being tested for the ability to elicit immune protection against M. tuberculosis or M. leprae challenge in animal model systems. The recombinants are also useful in generating target cells for assays aimed at elucidating the cellular immune responses to mycobacterial proteins in leprosy and tuberculosis. Furthermore, the M. tuberculosis 65-kDa protein and four of the other mycobacterial proteins share homology with known eucaryotic and procaryotic stress proteins, some of which may play a role in autoimmunity.

Animals

Clinical characteristics of acromegalic patients whose pituitary tumors contain mutant Gs protein.

Activating mutations in the gene for the alpha-chain of Gs, the stimulatory regulator of adenylyl cyclase, have been identified in human GH-secreting pituitary tumors. Using the polymerase chain reaction and allele-specific oligonucleotide hybridization, we screened 25 GH-secreting tumors for the presence of the activating mutations. We also reviewed the clinical charts of the patients from whom the tumors were removed. Of 25 tumors, 10 (40%) contained activating mutations. Patients in the mutation-positive group came to surgery with smaller tumors and had lower GH levels. The activating mutations identify a subgroup of GH-secreting pituitary tumors that probably arise from a shared oncogenic mechanism.

Acromegaly

High frequency of Ki-ras codon 12 mutations in pancreatic adenocarcinomas.

The frequency of Ki-ras gene mutations was studied in 100 paraffin-embedded sections obtained from 63 pancreatic adenocarcinomas by in vitro amplification of target sequences via polymerase chain reaction (PCR) and selective oligonucleotide hybridization. Forty-seven (75%) of the tumors contained a Ki-ras mutation at codon 12. No predominant amino acid substitution or nucleotide transition at this codon was observed. Two carcinomas exhibited 2 distinct Ki-ras mutations. No particular correlation could be established between the incidence of Ki-ras mutation and clinical parameters (sex, age, survival), tumor grade or tumor stage.

Adenocarcinoma