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Biomedical subjects

M Hayman

Publications and source records attributed to M Hayman.

At least 19 recordsLinked to original sources

Ski interacts with the evolutionarily conserved SNW domain of Skip.

Ski interacting protein (Skip) has been found to bind to the highly conserved region of Ski, which is required for its transforming activity. Ski is a unique oncoprotein that is involved in inducing both transformation and differentiation. At the molecular level, Ski has been shown to exhibit either co-activator or co-repressor activity depending on the cellular and promoter context. We were interested in further elucidating the biological implications of the Ski-Skip interaction. Here we have identified the SNW domain of Skip as the interaction region for Ski. This domain of Skip is highly conserved in all the Skip homologues identified from different species. Using a series of reporter plasmids, we show that Skip is a potent transcriptional activator of many different promoters, the activity of which was also mapped to the conserved core SNW domain of the protein. Addition of excess Ski further augmented the transcriptional activities of Skip, suggesting that one of the ways in which Ski brings about transformation is by binding and cooperating with the SNW domain of Skip in transcriptional activation.

Binding Sites↗

Postvaricella angiopathy: report of a case with pathologic correlation.

Varicella is a common childhood illness, and central nervous system complications occur frequently. Delayed angiopathy has been described, although there are few reports of clinicopathologic correlation. A previously well 4-year-old male is presented. He suffered varicella 2 months before presentation with extensive right middle cerebral artery (MCA) territory infarction. Cerebral angiography demonstrated an isolated 89% stenosis of the right proximal MCA. He developed cerebral edema refractory to medical treatment and progressed to transtentorial herniation. Right frontal temporoparietal craniotomies were performed with evacuation of infarcted brain tissue. Pathologic studies revealed small vessel vasculitis with lymphocytic infiltration of the vessel wall. Areas of demyelination were present within the white matter. Polymerase chain reaction for varicella was negative on brain tissue. Postvaricella angiopathy, although an uncommon complication, may affect both small and large blood vessels, with catastrophic results.

Cerebral Cortex↗

Plant glycerol-3-phosphate-1-acyltransferase (GPAT): structure selectivity studies.

Squash glycerol-3-phosphate-1-acyltransferase has been crystallized and the structure of the enzyme determined, at 1.9-A resolution, using multiple isomorphous replacement of the wild type and a series of individual cysteine mutants. Competitive in vitro substrate selectivity assays have been established that differentiate between selective and non-selective forms of the enzyme. Particular care was taken to use near-physiological concentrations of both substrates. Clear substrate selectivity can be demonstrated with the natural substrate acyl-acyl carrier protein but not with the substrate analogue acyl-CoA. The use of site-directed mutagenesis, coupled to three-dimensional structural determinations, should provide a rational basis for elucidating structural components important in determining the substrate selectivity of this enzyme.

Arabidopsis↗

Newborn radial nerve palsy: report of four cases and review of published reports.

Four newborns presented with isolated radial nerve palsy during the first 2 days of life. In three, there was a history of failure of progression of labor, which may have resulted in prolonged radial nerve compression. Furthermore, three infants had fat necrosis of the upper arm above the elbow, suggestive of compression of the radial nerve in the region of the spiral groove. Significant recovery of function was evident within 1 month in all four infants. The authors review published reports about the rare condition of isolated radial nerve palsy in the newborn.

Arm↗

Paroxysmal tonic upgaze: a reappraisal of outcome.

Paroxysmal tonic upgaze (PTU) of childhood is a distinctive neuro-ophthalmological syndrome of unknown etiology and pathogenesis that is characterized by episodes of sustained upward deviation of the eyes, often with incomplete downward saccades on attempted downgaze. It is generally regarded as having a benign outcome. We observed 16 children with PTU, from 10 months to 11 years from onset (mean, 5.4 years), to study the natural history and possible etiology. Five cases were from two unrelated families. Onset of PTU occurred either during or after an intercurrent infection or vaccination in 5 children. No antecedent was identifiable in the rest. PTU had completely resolved in 10 children (62%) (mean age at offset, 2.5 years), whereas 2 children intermittently manifest a modified form of the disorder. At follow-up, 11 children (69%) had developmental delay, intellectual disability, or language delay and 9 (56%) had ocular motility problems other than PTU. Only 3 children (19%) had normal development and neurological findings. PTU is a heterogeneous syndrome with respect to associations and outcome and may simply be an age-dependent manifestation of a variety of disorders affecting corticomesencephalic control of vertical eye movement. This disorder may be an early sign of more widespread neurological dysfunction.

Adolescent↗

Acromion-splitting approach through an os acromiale for repair of a massive rotator cuff tear.

Os acromiale, failure of fusion of the secondary centers of ossification of the acromion process, has been noted as a contributing factor in shoulder impingement syndrome and rotator cuff tears. Treatments for symptomatic os acromiale with or without rotator cuff tears have been reported in the literature and range from excision of small fragments to fusion of larger, fragments with internal fixation and bone grafting. Generally, rotator cuff repairs have been performed when possible. We report an acromion splitting approach through an existing os acromiale to gain exposure for the repair of a massive rotator cuff tear. Subsequent to this repair, the acromion was repaired with internal fixation. Good functional use of the patient's upper extremity was obtained and the patient expressed satisfaction with the surgical outcome. The acromion splitting approach is a viable approach in patients with an os acromiale and a coexistent rotator cuff tear.

Acromion↗

Autosomal dominant nocturnal frontal lobe epilepsy: demonstration of focal frontal onset and intrafamilial variation.

Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a newly recognized autosomal dominant partial epilepsy. We studied seizure localization and intrafamilial variation using video-EEG monitoring (VEM) and functional neuroimaging in two pairs of subjects from unrelated families. The clinical features of seizures were similar from seizure to seizure in each individual, but varied between individuals. As is often found in frontal lobe epilepsies, ictal EEG localization was imprecise in three of four cases. One patient showed a consistent left fronto-polar onset that was corroborated by congruent focal hypometabolism on interictal PET and focal hyperperfusion on ictal single photon emission computed tomography (SPECT). A second case studied with ictal SPECT showed a right parasagittal, midfrontal focus. We conclude that this autosomal dominant epilepsy syndrome, which in one of the two families was due to a known neuronal nicotinic acetylcholine receptor mutation, causes frontal lobe foci that are unilateral and in variable locations in different individuals.

Adolescent↗

Applying physiological principles and assessment techniques to swimming the English Channel. A case study.

BACKGROUND: This study presents the use of physiological principles and assessment techniques in addressing four objectives that can enhance a swimmer's likelihood of successfully swimming the English Channel. The four objective were: (1) to prescribe training intensities and determine ideal swimming pace; (2) to determine the amount of insulation needed, relative to heat produced, to diminish the likelihood of the swimmer suffering from hypothermia; (3) to calculate the caloric expenditure for the swim and the necessary glucose replacement required to prevent glycogen depletion; and (4) to determine the rate of acclimatization to cold water (15.56 C/60 F). METHODS: The subject participated in several pool swimming data collection sessions including a tethered swim incremental protocol to determine peak oxygen consumption and onset of lactate accumulation and several steady state swims to determine ideal swimming pace at 4.0 mM/L of lactate. Additionally, these swims provided information on oxygen consumption, which in combination with ultrasound assessment of subcutaneous fat was used to assess heat production and insulation capabilities. Finally, the subject participated in 18 cold water immersions to document acclimatization rate. RESULTS: The data demonstrated the high fitness level of this subject and indicated that at a stroke rate of 63 stokes/min, HR was 130 heats/min and lactate was 4 mM/L. At this swimming pace the swimmer would need to consume 470 kcal of glucose/hr. In addition, the energy produced at this swim pace was 13.25 kcal/min while the energy lost at the present subcutaneous fat quantity was 13.40 kcal/min, requiring a fat weight gain of 6,363.03 g (13.88 lbs) to resist heat loss. CONCLUSIONS: Finally, the data from the cold water immersions suggested that acclimatization occurred following two weeks of immersions. There results were provided to the swimmer and utilized in making decisions in preparation for the swim.

Acclimatization↗

Neurotoxicity of peptide analogues of the transactivating protein tat from Maedi-Visna virus and human immunodeficiency virus.

Infection by lentiviruses such as human immunodeficiency virus, Maedi-Visna virus and Caprine Arthritis Encephalitis Virus, is associated with a variety of neurological syndromes, but the mechanism by which the damage occurs to the nervous system is not known. The viruses do not infect neurons and so the neurotoxic actions must be mediated indirectly. Here we applied synthetic peptide analogues derived from basic regions of Maedi-Visna virus and human immunodeficiency virus transactivating protein, tat, to rat brain in vivo and found them to be potent neurotoxins. The toxicity of the Maedi-Visna virus peptide was demonstrated to be reduced by blockade of nitric oxide synthase and of N-methyl-D-aspartate channel opening. These experiments suggest that peptides derived from lentiviral tat may share a common neurotoxic action.

Amino Acid Oxidoreductases↗

The fibroblast growth factor receptor 3 gene (FGFR3) is assigned to human chromosome 4.

Fibroblast growth factor receptors (FGFRs) have recently been isolated and shown to be transmembrane tyrosine kinase receptors. The FGFR1 gene has previously been assigned to human chromosome 8 and the FGFR4 gene to human chromosome 5. Here we demonstrate, by using somatic cell hybrids, that the FGFR3 gene localizes to human chromosome 4, showing that it, too, resides on a chromosome distinct from those on which other FGFRs have been localized.

Animals↗

Molecular cloning of the chicken myelomonocytic growth factor (cMGF) reveals relationship to interleukin 6 and granulocyte colony stimulating factor.

Normal as well as retrovirally transformed avian myeloid precursor cells require the colony stimulating factor cMGF for their survival, proliferation and colony formation in vitro. cMGF has been shown to be a glycoprotein which is active in the picomolar concentration range. Co-expression of kinase type oncogenes in v-myb or v-myc transformed myeloid cells induces cMGF expression and confers factor independence via an autocrine mechanism. Here we describe the molecular cloning of cMGF from a myeloblast cDNA library and show that it is a 201 amino acid residue secretory protein which is modified by signal peptide cleavage and glycosylation during translocation into the lumen of membrane vesicles. A bacterially expressed trpE-cMGF fusion protein induces proliferation of E26 transformed myeloblasts in a cMGF bioassay suggesting that glycosylation is not absolutely necessary for biological activity. Sequence comparison reveals that cMGF is distantly related to G-CSF and IL-6.

Amino Acid Sequence↗

Two new retroviral onc genes, sea and jun.

Avian leukemia virus S13 induces erythroblastosis, granulocytic leukemia, fibrosarcoma, anemia, and endothelial neoplasia. It transforms chick embryo fibroblasts and primitive erythroid cells in culture and is defective in replication. Its onc gene, sea, is expressed as transformation specific env-sea fusion glycoprotein of 155 kDa. Gp155 is proteolytically processed into gp85env and gp70env-sea. The latter shows tyrosine specific protein kinase activity. Avian sarcoma virus 17 induces fibrosarcoma and transforms chick embryo fibroblasts in culture. Its cell derived onc gene, jun, is not related to known onc genes and appears to be expressed as a gag-jun fusion protein of 55 kDa. The amino acid sequence of jun shows homology in its C-terminal region to the C-terminal DNA binding region of the yeast regulatory protein GCN4, suggesting that the jun protein may bind to DNA.

Amino Acid Sequence↗

Comparison of genome structures among three different strains of avian erythroblastosis virus.

The genomic DNAs of two strains of avian erythroblastosis virus (AEV), AEV-R and AEV-H, were molecularly cloned in Escherichia coli using lambda Charon 16A as a vector. Comparison of the restriction maps of the cloned DNAs with that of AEV-ES4 DNA revealed that R strain is identical with ES4 strain, but totally differs from H strain. The erbB gene product of AEV-R and that of AEV-H were shown to be glycoproteins with molecular weights of 68,000 and 72,000, respectively. Nucleotide sequence analysis of the 3' part of the erbB gene showed that the erbB gene in AEV-R is 126 base pairs (bp) shorter than that in AEV-H, which might result in some difference in tumorigenicity between these viruses.

Alpharetrovirus↗