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Biomedical subjects

R Goodman

Publications and source records attributed to R Goodman.

At least 109 records · Page 6Linked to original sources
PubMed1990

A direct role for c-fos in AP-1-dependent gene transcription.

Transcription factor activator protein 1 (AP-1) is a protein fraction that contains c-fos, c-jun, and several other related proteins. Although this protein fraction can stimulate transcription in vitro, the relative contributions of c-fos and c-jun to the transcriptional effect of AP-1 are not clear. In order to approach this question, we have overexpressed both proteins using a baculovirus-mediated expression system and defined their DNA-binding and transcriptional enhancement activities in vitro. Gel mobility-shift and DNase 1 footprinting assays showed that c-jun protein specifically binds to DNA through an AP-1 binding site. Under the same conditions, no detectable binding of c-fos protein was observed. However, when the DNA binding assays were performed in the presence of both c-jun and c-fos, a marked increase in the affinity of c-jun for the AP-1 site was observed. An AP-1-dependent transcription assay was used to test the capability of both proteins to stimulate correctly initiated RNA synthesis in vitro. Under our conditions, c-jun protein was capable of stimulating specific RNA transcription in an AP-1 site-dependent manner. In contrast, c-fos protein showed no detectable transcriptional activation by itself. However, a transcription assay carried out in the presence of both c-fos and c-jun proteins showed that the c-fos/c-jun complex was more active as a transcriptional regulator than c-jun protein alone. These experimental results indicate that c-fos and c-jun proteins are required to reconstitute full AP-1-dependent transcriptional activation and directly demonstrate that c-fos is a regulator of gene expression.

Animals↗
PubMed1990

Reliability of measurements of active and damaged joints in psoriatic arthritis.

Our aim was to test the reliability of clinical measurements in psoriatic arthritis. The study involved clinical assessments of inflammatory activity as well as damage in 10 patients with psoriatic arthritis seen at the psoriatic arthritis clinic. Five rheumatologists examined these patients according to a latin square design. For the clinical measurements of actively inflamed joints and damaged joints there was no significant observer effect. This suggests that these are reliable measurements. There was, however, significant observer effect in the radiologic assessment, and further refinement of the measurement is required.

Arthritis, Psoriatic↗
PubMed1989

Exposure of human cells to low-frequency electromagnetic fields results in quantitative changes in transcripts.

The exposure of human cultured cells to electromagnetic signals with extremely low repetition rates resulted in an increased level of selected RNA transcripts. RNA with homology to beta-actin, histone H2B, and v-myc DNA was monitored by dot blot hybridization following 20 min exposures of HL60 cells to five different electromagnetic signals. The experiments used three asymmetric electromagnetic signals with different repetition rates, and two symmetric sinusoidal signals, delivered at 60 and 72 Hz. The degree of increase in homologous transcripts was dependent on the signal characteristics.

Actins↗
PubMed1989

Infantile autism: a syndrome of multiple primary deficits?

Attempts to explain infantile autism in terms of just one underlying neurological or psychological deficit may be misguided. As in the case of many neurological syndromes, autism may involve multiple functional deficits due to multiple coexistent neurological deficits. Comparison with Asperger's syndrome and the developmental dysphasias suggests that the autistic syndrome results from the coexistence of at least two distinct constellations of functional impairments: deficits in mechanical language skills, as in the developmental dysphasias; and deficits in social relatedness, play, and nonverbal communication, as in Asperger's syndrome. Possible neurological underpinnings are considered, including the relative contribution of the two cerebral hemispheres. Implications for etiology and research are discussed.

Aphasia↗
PubMed1989

A twin study of hyperactivity--I. An examination of hyperactivity scores and categories derived from Rutter teacher and parent questionnaires.

In a representative sample of 570 13-yr-old twins, higher hyperactivity scores from parent and teacher ratings were associated with male sex, lower intelligence, inattention, specific learning problems, and behavioural deviance (mainly antisocial). This pattern of correlates also characterized all three hyperactivity categories: to a marked degree in pervasive hyperactivity; less markedly in school hyperactivity; and least markedly in home hyperactivity. Children with pervasive hyperactivity had more attentional and educational problems than non-hyperactive children who were pervasively antisocial. By contrast, children with school or home hyperactivity resembled non-hyperactive children who were situationally antisocial. These findings cast doubt on the validity of combining situational and pervasive hyperactivity into a single diagnostic category such as Attentional Deficit Disorder with Hyperactivity (ADDH).

Adolescent↗
PubMed1989

A twin study of hyperactivity--II. The aetiological role of genes, family relationships and perinatal adversity.

In a large representative sample of 13-year-old twins, monozygotic pairs were more alike than same-sex dizygotic pairs on objective measures of attentiveness and on parent and teacher ratings of hyperactivity. Comparison of recognized and unrecognized monozygotic pairs indicated that parents and teachers rated twins more similarly when the twins were perceived as "identical" rather than "non-identical". After allowing for this stereotyping, genetic effects accounted for approximately half of the explainable variance of hyperactivity and inattentiveness. Data from mixed-sex pairs did not support a 2-threshold genetic explanation for the male excess of hyperactivity. The link between adverse family factors and hyperactivity was weak. Perinatal adversity was not related to later hyperactivity.

Adolescent↗
PubMed1989

Neuronal misconnections and psychiatric disorder. Is there a link?

Brain damage can induce anomalous neuronal connections in experimental animals, which can sometimes result in maladaptive behaviour, particularly when damage occurs early in development. Anomalous patterns of neuronal connection can also arise from genetic disorders. In humans, neuronal misconnections could be involved in a variety of psychiatric disorders. For example, they may account for the link between hyperkinesis and childhood hemiplegia, and for the link between schizophrenia and 'alien tissue' lesions of the temporal lobes. Predictions from misconnection hypotheses can potentially be tested in neuropathological, neurophysiological, and clinical studies.

Brain↗
PubMed1989

Successive unfolding of two different collagen vascular diseases in the same patient.

Genetic factors may be important in the development of autoimmune disease. We describe the development of fulminant systemic lupus erythematosus in a patient 5 years after recovery from polymyositis. The successive unfolding of different autoimmune diseases in the same individual is suggestive of sequential gene activation.

Antibodies, Antinuclear↗
PubMed1988

Kinetic analysis of an E.coli phenylalanine-tRNA synthetase mutant.

A mutation in the pheS gene, encoding phenylalanyl-tRNA synthetase, in E. coli NP37 confers temperature-sensitivity on the organism. A five-fold increase in tRNA(phe) levels complements the mutation. Analysis of the kinetic properties of the mutant enzyme indicates that the KM is 20-fold higher than the wild-type and the dissociation constant of the tRNA(phe)-synthetase complex for the mutant is at least 10-fold higher. These results indicate that the mutation in E. coli NP37 directly affects the tRNA(phe) binding site on the cognate synthetase.

Amino Acyl-tRNA Synthetases↗
PubMed1988

Radiotherapy for the prevention of local-regional recurrence in high risk patients post mastectomy receiving adjuvant chemotherapy.

From 1977 to 1986, 63 patients at high risk for isolated local-regional recurrence following mastectomy and adjuvant chemotherapy received post-operative radiotherapy. All patients had operable primary tumors (T1-3a). For entire group the mean and median number of positive nodes were 10 and 8, respectively. Radiotherapy consisted of 4500 to 5000 rad to the chest wall and regional nodes. Chemotherapy consisted of CMF +/- prednisone (45 patients), CAF (16 patients), and other variable regimens (2 patients). Relapse occurred in 23 patients with only two patients experiencing an isolated local-regional recurrence. In 3 patients local-regional recurrence appeared simultaneously with or following distant metastases and in 18 patients the pattern of failure was distant metastases alone. With a median follow-up of 28 months (range 9-87 mo.), 40 patients are alive without disease, 9 are alive with disease, and 14 have died with disease. The 4-year actuarial overall survival is 67% and the 4-year actuarial disease-free survival is 47%. The 4-year actuarial probability of an isolated local-regional recurrence is 5%. Complications related to the radiation included a 9% incidence of moderate to severe arm edema. This study demonstrates the ability of radiation to reduce the incidence of local-regional recurrence in a previously identified high risk group of patients and has produced encouraging survival results with minimal morbidity.

Actuarial Analysis↗
PubMed1988

Exposure of salivary gland cells to low-frequency electromagnetic fields alters polypeptide synthesis.

This study demonstrates that exposure of cells to extremely low-frequency electromagnetic fields can cause measurable changes in protein synthesis. Sciara coprophila salivary gland cells were exposed to five low-frequency (1.5-72 Hz) electromagnetic signals: three signals (1.5, 15, and 72 Hz) produced pulsed asymmetric electromagnetic fields and two signals (60 and 72 Hz) were sinusoidal. Subsequent analyses of two-dimensional gels showed that cell exposure to either type of low-frequency electromagnetic field resulted in both qualitative and quantitative changes in patterns of protein synthesis. Thus, signals producing diverse waveform characteristics induced previously undetectable polypeptides, some of which were signal specific and augmented or suppressed other polypeptides as compared with nonexposed cells. The pattern of polypeptide synthesis differed from that seen with heat shock: only five polypeptides in cells exposed to electromagnetic signals overlap those polypeptides exposed to heat shock, and the suppression of protein synthesis characteristic of heat shock does not occur.

Animals↗
PubMed1987

Genomic organization and deduced amino acid sequence of a putative sodium channel gene in Drosophila.

The deduced amino acid sequence of a Drosophila gene isolated with a vertebrate sodium channel complementary DNA probe revealed an organization virtually identical to the vertebrate sodium channel protein; four homologous domains containing all putative membrane-spanning regions are repeated in tandem with connecting linkers of various sizes. All areas of the protein presumed to be critical for channel function show high evolutionary conservation. These include those proposed to function in voltage-sensitive gating, inactivation, and ion selectivity. All 24 putative gating charges of the vertebrate protein are in identical positions in the Drosophila gene. Ten introns interrupt the coding regions of the four homology units; introns with positions conserved among homology units bracket a region hypothesized to be the selectivity filter for the channel. The Drosophila gene maps to the right arm of the second chromosome in region 60D-E. This position does not coincide with any known mutations that confer behavioral phenotypes, but is close to the seizure locus (60A-B), which has been hypothesized to code for a voltage-sensitive sodium channel.

Amino Acid Sequence↗
PubMed1987

Transcriptional patterns in the X chromosome of Sciara coprophila following exposure to magnetic fields.

We previously demonstrated that exposure of salivary gland cells of the dipteran, Sciara coprophila, to either asymmetrical or symmetrical changing magnetic fields results in an increase in the incorporation of radioactive uridine into RNA. The present report is an analysis of the grain count distribution over the X chromosome of Sciara in transcription autoradiograms following exposure of the salivary gland cells to two pulsed magnetic signals and a 72-Hz sine wave signal. The results show augmented uptake of 3H-uridine into nascent RNA chains following short exposures of the cells to magnetic fields. Transcription is augmented in previously active loci, as well as at chromosome regions that are not detectable as active in control cells. The quantitative pattern of RNA synthesis in transcription autoradiograms is hypothesized to be signal specific on the basis of differences in grain counts over significantly labelled chromosome sites.

Animals↗