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Biomedical subjects

S Brennan

Publications and source records attributed to S Brennan.

At least 73 records · Page 4Linked to original sources
PubMed1986

Nerve conduction studies in the Twitcher mouse (murine globoid cell leukodystrophy).

Progression of the neuropathy in the Twitcher mouse (twi-C57BL/6J), an animal model of globoid cell leukodystrophy, was assessed with serial motor nerve conduction studies from just after birth until near death (day 45) and after hematopoietic cell transplantation (HCT). Under ether anesthesia, the tibial nerve was stimulated percutaneously at the sacral notch and at the ankle, and recordings were made from plantar foot muscles. Motor conduction velocity (MCV), distal latency, amplitude, duration and number of phases of compound muscle action potentials on proximal (pCMAP) and distal (dCMAP) stimulation were measured. In 15-19 day-old Twitcher, despite the absence of motor signs, MCV was significantly reduced, 12.8 +/- 2.8 (10) m/s (M +/- SD, No. of recordings), compared with unaffected siblings, 18.1 +/- 2.6 (21) m/s (P less than 0.01). The ratio of pCMAP to dCMAP amplitudes was reduced in the Twitcher, 0.39 +/- 0.13 (10), compared with controls 0.72 +/- 0.17 (21) and the ratio of pCMAP to dCMAP phases was increased (2.8 +/- 0.8 (10) vs 1.0 +/- 0.2 (21), P less than 0.01 for all). As neurologic signs progressed by 35-39 days, MCV became slower, 5.8 +/- 1.0 (11) m/s, pCMAP and dCMAP became smaller, but the ratio of pCMAP to dCMAP amplitudes in the Twitcher (0.55 +/- 0.36, 11) was similar to controls (0.71 +/- 1.0, 20) as was the ratio of pCMAP to dCMAP phases (1.0 +/- 0.4 vs 1.0 +/- 0.1). These results suggest that there is diffuse non-uniform slowing of nerve conduction with block especially in proximal nerve fibers initially. With HCT, mean MCV remained slow (6.7 +/- 1.2 (18) m/s, vs 34.5 +/- 3.9 (12) m/s) but motor function persisted.

Age Factors↗
PubMed1986

The effects of benzamide ADP-ribosyl transferase inhibitors on cell survival and DNA strand-break repair in irradiated mammalian cells.

We have recently shown that 3-acetamidobenzamide (3-AAB), a highly effective inhibitor of ADP-ribosyl transferase (ADPRT), can act as a post-irradiation (electrons) sensitizer on the mouse lymphoma cell lines L5178Y R and S. We have now shown that this compound sensitizes human derived skin fibroblasts but to a lesser extent. Fibroblasts derived from normal, Friedreich's ataxia, and ataxia-telangiectasia individuals were equally sensitized by 3-AAB to electron radiation. 3-AAB was also effective in sensitizing the mouse lymphoma lines to fast neutron irradiation. In addition DNA strand break repair was retarded as had been found after electron irradiation. 3-Nitrobenzamide is structurally a potentially dual action radiation sensitizer with electron affinic and ADPRT inhibitory properties. It is a weaker inhibitor of ADPRT compared to 3-AAB, and results in a smaller sensitization of mouse lymphoma cells in air. However, a much greater sensitization is achieved in anoxia. This greater sensitization appears to be a synergistic rather than an additive combination of its electron affinic and ADPRT inhibitory properties.

Animals↗
PubMed1985

A therapeutic trial of amniotic epithelial cell implantation in patients with lysosomal storage diseases.

To determine whether allografts of normal amniotic epithelium might provide a nonimmunogenic cellular source of exogenous lysosomal enzymes, subcutaneous implants of amniotic epithelium were performed in six children with clinically advanced storage diseases. The clinical and the biochemical status of each patient was observed for several weeks after amniotic epithelial cell implantation (AECI). Serial studies of blood samples from each patient in the post-AECI period did not demonstrate any increase in levels of deficient lysosomal hydrolase. In two patients, quantitative urinary excretion of substrate was also studied and did not show consistent alterations after AECI. No patient had objective improvement in clinical or neurodevelopmental status following AECI. Two patients died with progressive disease at 2 1/2 and 3 1/2 mo after AECI; no residual amniotic epithelium was found at postmortem examination. Four patients are alive with progressive disease at 6-14 mo after AECI. We conclude that allografts of normal human amnion do not provide sufficient replacement hydrolases for clinical or biochemical improvement in lysosomal storage diseases.

Amidohydrolases↗
PubMed1985

Activation of muscle-specific actin genes in Xenopus development by an induction between animal and vegetal cells of a blastula.

Muscle gene expression is induced a few hours after vegetal cells of a Xenopus blastula are placed in contact with animal cells that normally develop into epidermis and nerve cells. We have used a muscle-specific actin gene probe to determine the timing of gene activation in animal-vegetal conjugates. Muscle actin RNA is first transcribed in a minority of animal cells at a stage equivalent to late gastrula. The time of muscle gene activation is determined by the developmental stage of the responding (animal) cells, and not by the time when cells are first placed in contact. The minimal cell contact time required for induction is between 1 1/2 and 2 1/2 hr, and the minimal time for gene activation after induction is 5-7 hr.

Actins↗
PubMed1985

All components required for the eventual activation of muscle-specific actin genes are localized in the subequatorial region of an uncleaved amphibian egg.

Fertilized Xenopus eggs have been ligated with a hair loop into separate fragments before the first cleavage. The plane of the ligation was varied in relation to the animal-vegetal and dorso-ventral axes. The fragments that contained a nucleus were cultured for 24 hr until controls reached the neurula stage; they were then analyzed by S1 nuclease protection for their content of muscle-specific actin mRNA, using a gene-specific probe. We find that all egg components required for the eventual activation of these actin genes are localized, already at the 1-cell stage, in a region below the equator, and mostly on the dorsal (grey crescent) side. This material subsequently occupies the equivalent position in 8-cell and 32-cell embryos. We interpret our results, in combination with the previous work of others, to mean that mesoderm (including muscle) formation in Amphibia depends both on cytoplasmic substances already localized in the egg as well as on inductive cell interactions during cleavage.

Actins↗
PubMed1985

Actin genes in Xenopus and their developmental control.

The results summarized here have established the temporal and regional activation of three kinds of Xenopus actin genes. The cardiac and skeletal muscle actin genes are among the first cell-type-specific genes to be expressed in early development. The first transcripts to be synthesized by these genes appear to be correctly initiated, spliced, and at once translated into proteins. Both cardiac and skeletal actin genes are strongly transcribed in the axial skeletal muscle of embryos. The mechanism by which the cardiac actin gene is first transcribed in only the somite region of an embryo depends, at least in part, on materials already localized in the subequatorial region of a fertilized but uncleaved egg. Cells which acquire this material seem able to activate their cardiac actin genes without requiring normal contact with other cells.

Actins↗
PubMed1984

Region-specific regulation of the actin multi-gene family in early amphibian embryos.

The actin multi-gene family shows both spatial and temporal regulation during early embryogenesis in the amphibian Xenopus laevis. Both muscle-specific and ubiquitous cytoskeletal actin genes are activated at the end of gastrulation; transcription of the alpha-cardiac and alpha-skeletal actin genes is restricted to the somitic mesoderm and its muscle-forming derivatives providing a convenient molecular marker for this early embryonic tissue.

Actins↗
PubMed1984

Prolonged survival and remyelination after hematopoietic cell transplantation in the twitcher mouse.

The twitcher mouse is an animal model of galactosylceramidase deficiency (Krabbe's disease), a human sphingolipidosis. The effects of hematopoietic cell transplantation as potential enzyme replacement therapy were examined in the twitcher mouse. Survival in twitcher mice with transplants was significantly prolonged and was associated with gradual repair of demyelination in peripheral nerves. In contrast, there was no improvement in the neurodegenerative process in the central nervous system after transplantation. These observations indicate that cellular transplantation may effectively provide in vivo enzyme replacement for the peripheral manifestations of genetic storage diseases. Strategies to perturb the blood-brain barrier may be necessary for enzyme replacement to be therapeutic in diseases with central nervous system manifestations.

Animals↗
PubMed1984

Transcription of muscle-specific actin genes in early Xenopus development: nuclear transplantation and cell dissociation.

Cloned cDNA probes that recognize muscle-specific alpha-actin gene transcripts have been used to analyze two kinds of experimental embryos in Xenopus. In one, genetically marked nuclei of larval muscle cells were transplanted to wild-type enucleated eggs; alpha-actin genes became transcriptionally inactive in the resulting blastulae but were reactivated when these embryos reached the normal stage of alpha-actin expression (late gastrula). In the other, blastula embryos reared from fertilized eggs were separated into animal, vegetal, and equatorial regions, and their cells dissociated and reaggregated. alpha-Actin RNA was synthesized at the normal time in development, but only by equatorial cells. We conclude that alpha-actin gene transcription is normally regulated in nuclear-transplant embryos and is undisturbed by the absence of cell contacts during cleavage.

Actins↗
PubMed1983

Studies of cellular radiosensitivity in hereditary disorders of nervous system and muscle.

Skin fibroblasts from patients with familial dysautonomia, Duchenne muscular dystrophy and Charcot-Marie-Tooth disease show normal sensitivity to ionising radiation, as measured by post-irradiation clonal growth. Previous reports of cellular hypersensitivity to ionising radiation and other DNA-damaging agents in familial dysautonomia and Duchenne muscular dystrophy have not been confirmed.

Adolescent↗
PubMed1983

Radioimmunometric assay for a monoclonal antibody-defined tumor marker, CA 19-9.

We describe a solid-phase radioimmunometric sandwich assay for a new tumor marker defined by a monoclonal antibody (19-9). This antibody reacts with a carbohydrate antigenic determinant (CA 19-9) found at low concentrations in sera from healthy individuals but frequently increased in sera from patients with adenocarcinomas. The assay is sensitive and simple to perform. It requires duplicate 100-microL samples and may be performed in 6 h. The concentration of CA 19-9 in samples is determined by reference to a standard curve, which is essentially linear from 0 to 120 arbitrary units/mL. The average CV is approximately 10% in the range of 5.8 to 120 units/mL. The minimum detectable dose is 1.4 units/mL and analytical recovery of CA 19-9 is 97.6 to 100.6%. The average concentration of CA 19-9 in sera from 1020 healthy individuals was 8.4 (SD 7.4) units/mL; only 0.6% of such sera had concentrations greater than 37 units/mL. The assay has high specificity (98.5%), even among patients with benign diseases, and has high sensitivity (up to 79%) for patients with gastrointestinal adenocarcinomas, especially those of the pancreas.

Adenocarcinoma↗
PubMed1977

A new hybrid haemoglobin: haemoglobin Strumica/Beograd occurring in an individual with four haemoglobins.

An investigation of the cord blood from full term twin infants revealed an additional haemoglobin F component due to an abnormal alpha chain. The father of the twins, whose blood picture was normal, was shown to have normal alpha and beta polypeptide chains together with variant alpha and beta polypeptide chains. Electrophoresis showed that he had four major haemoglobin components. Separation of the haemoglobin fractions by column chromatography, globin preparation, chain separation, tryptic and chymotryptic digestion and peptide map preparation led to the identification of haemaglobin A, haemoglobin Strumica (alpha2 112His leads to Arg beta2), haemoglobin D Beograd (alpha2beta2 121 Glu leads to Val) and a hybrid haemoglobin Strumica D/Beograd (alpha2 112His leads to Argbeta2 121Glu leads to Val).

Alleles↗
PubMed1975

Trial of long-term anticoagulant therapy in the treatment of small stroke associated with a normal carotid arteriogram.

The clinical features of 49 patients who had sustained small strokes in the internal carotid artery territory, who were normotensive, free from cardiac or other relevant disease, and who each had a normal appropriate single vessel angiogram are presented. These were randomized into two groups: group A, 25 patients, who received only supportive treatment; group B, 24 patients who were treated with anticoagulants for an average period of 18 months. There was a reduced incidence of neurological episodes during the administration of anticoagulant therapy but, after treatment was discontinued, there was no significant difference between the two groups. In view of the relatively benign prognosis for this syndrome, unless special facilities exist for the personal control of anticoagulant treatment, the dangers may outweigh the benefits.

Adult↗
PubMedDate not supplied

Cell type-specific activation of actin genes in the early amphibian embryo.

Muscle actin genes are the earliest yet described to show cell type-specific activation in amphibian embryos. Gene-specific probes show that alpha-skeletal and alpha-cardiac actin genes start to be transcribed simultaneously at the end of gastrulation, but only in those regions of the mesoderm that subsequently form embryonic muscle. Their expression provides a molecular marker for early cell determination.

Actins↗