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Biomedical subjects

A M Taylor

Publications and source records attributed to A M Taylor.

At least 163 records · Page 9Linked to original sources
PubMed1987

Variant forms of ataxia telangiectasia.

Two ataxia telangiectasia patients with unusual clinical and cellular features are described. Cultured fibroblasts and PHA stimulated lymphocytes from these two patients showed a smaller increase of radiosensitivity than cells from other A-T patients, as measured by colony forming ability or induced chromosome damage respectively, after exposure to ionising radiation. The response of DNA synthesis to irradiation of these cells was, however, the same as for other A-T patients. Cells from a third patient with some clinical features of A-T but with a very protracted course also showed low levels of radiation induced chromosome damage, but colony forming ability and the response of DNA synthesis after irradiation were no different from cells of normal subjects. There was, however, an increased level of translocations and unstable chromosomal rearrangements in this patient's lymphocytes.

Adolescent↗
PubMed1987

Inhibition of somatomedin-like activity by serum from streptozotocin-diabetic rats: prevention by insulin treatment and correlation with skeletal growth.

Diabetes mellitus was induced in rats by streptozotocin. This gave rise to a loss of somatomedin activity in serum. The loss of somatomedin activity was due to the presence of inhibitors associated with serum proteins having mol wts of less than 1, 1-10, 30-50, and 300 K. Whereas less than 1, 1-10, and 30-50 kilodalton fractions were not inhibitory in control and insulin-treated animals, greater than 300 kilodalton fraction was inhibitory in control and insulin-treated animals; the inhibitory activity of this fraction in diabetic animals was significantly greater than that in controls and insulin-treated animals. The appearance of these inhibitors in diabetic animals was accompanied by reduced skeletal growth. Treatment of diabetic animals with insulin abolished the somatomedin-inhibitory activity of serum and corrected the skeletal growth deficit. Serum inhibitors of somatomedin may, therefore, be involved in the causation of some of the complications of diabetes, including impaired skeletal growth.

Animals↗
PubMed1986

Clonal evolution of T-cell chronic lymphocytic leukaemia in a patient with ataxia telangiectasia.

Ataxia telangiectasia (A-T) is an autosomal recessive disorder in which patients show an unusual predisposition to malignant disease, including T-cell chronic lymphocytic leukaemia. We report here the steady growth over 5 years of a complex, cytogenetically abnormal clone of T lymphocytes in an A-T patient who was subsequently found to have an OKT3/OKT8 chronic lymphocytic leukaemia. The tumour cells at diagnosis had clearly evolved from a pre-existing, cytogenetically abnormal T-cell clone which contained an inv(14) chromosomal inversion alone.

Ataxia Telangiectasia↗
PubMed1986

Subcortical afferent and efferent connections of the superior colliculus in the rat and comparisons between albino and pigmented strains.

Subcortical connections of the superior colliculus were investigated in albino and pigmented rats using retrograde and anterograde tracing with horseradish peroxidase (HRP), following unilateral injection of HRP into the superior colliculus. Afferents project bilaterally from the parabigeminal nuclei, the nucleus of the optic tract, the posterior pretectal region, the dorsal part of the lateral posterior-pulvinar complex and the ventral nucleus of the lateral lemniscus; and ipsilaterally from the substantia nigra pars reticulata, the pars lateralis of the ventral lateral geniculate nucleus, the intergeniculate leaflet, the zona incerta, the olivary pretectal nucleus, the nucleus of the posterior commissure, the lateral thalamus, Forel's field H2, and the ventromedial hypothalamus. Collicular efferents terminate ipsilaterally in the anterior, posterior and olivary pretectal nuclei, the nuclei of the optic tract and posterior commissure, the ventrolateral part of the dorsal lateral geniculate nucleus, the pars lateralis of the ventral lateral geniculate nucleus, the intergeniculate leaflet, and the zona incerta; and bilaterally in the parabigeminal nuclei and lateral posterior-pulvinar complex (chiefly its dorsal part). The general topographical patterns of some of the afferent and efferent projections were also determined: the caudal and rostral parts of the parabigeminal nucleus project to the caudal and rostral regions, respectively, of the superior colliculus; caudal superior colliculus projects to the most lateral, and lateral superior colliculus to the most caudal part of the terminal field in the dorsal lateral geniculate nucleus; caudolateral superior colliculus projects to the caudal ventrolateral part of the ventral lateral geniculate nucleus, while rostromedial parts of the colliculus project more rostrally and dorsomedially. Following comparable injections in pigmented and albino animals, fewer retrogradely labelled cells were found in subcortical structures in the albino than in the pigmented rats. The difference was most marked in nuclei contralateral to the injected colliculus. Thus, the effects of albinism on the nervous system may be more widespread than previously thought.

Albinism↗
PubMed1986

A subpopulation of t(2;14)(p11;q32) cells in ataxia telangiectasia B lymphocytes.

Partially purified B cells from ataxia telangiectasia (A-T) patients and normal individuals were stimulated with Staphylococcus aureus Cowan I organisms (SAC). High levels of apparently random rearrangements were seen in the A-T B cells only. In addition a t(2;14)(p11;q32) rearrangement was identified in B cells from more than one patient.

Ataxia Telangiectasia↗
PubMed1986

The chromosome breakpoint at 14q32 in an ataxia telangiectasia t(14;14) T cell clone is different from the 14q32 breakpoint in Burkitts and an inv(14) T cell lymphoma.

The T cell receptor alpha chain gene locus and the immunoglobulin heavy chain gene locus (IgH) have previously been mapped to the q11 and q32 positions respectively of the human chromosome 14. Both of these sites are also common breakpoints in lymphocytes from ataxia telangiectasia (A-T) patients. Using in situ hybridisation we show that the 14q32 breakpoint in an A-T non-leukaemic T cell clone with t(14;14) translocation, lies outside the IgH locus and proximal to it with respect to the centromere. The 14q11-14qter segment of the homologous chromosome 14 carrying the constant gene region of the alpha chain locus is translocated to this 14q32 position.

Ataxia Telangiectasia↗
PubMed1986

Human plasma fractions inhibit the action of insulin on adipocytes and somatomedin on cartilage.

Since human immunoglobulins exert an insulin-like stimulatory effect on adipocyte lipogenesis at concentrations markedly lower than those found in vivo, and since human serum or plasma are only midly stimulatory, we predicted that human serum probably contains an inhibitor of adipocyte lipogenesis. Supernatant preparations, obtained from the precipitation of immunoglobulins from plasma in 2.5 mol/l ammonium sulphate, were extensively dialysed and tested for their activity on bioassay systems commonly used for measuring insulin. The supernatants produced a marked inhibition of basal and insulin- or IgG-stimulated lipogenesis and glucose oxidation by adipocytes at protein concentrations of 10 mg/l. The supernatants were further purified through ultrafiltration to demonstrate two main inhibitory fractions, 10 to 30 K and 30 to 50 K, which again produced marked inhibition of basal and insulin- or IgG-stimulated adipocyte lipogenesis and glucose oxidation. These fractions were then tested for basal and serum somatomedin-stimulated 35S sulphate uptake by porcine cartilage: both basal and serum somatomedin-stimulated 35S uptake were significantly inhibited (p less than 0.01). Therefore, normal human serum contains at least two peptides which are markedly inhibitory to glucose metabolism and insulin action on adipocytes and 35S transport and somatomedin action on cartilage.

Adipose Tissue↗
PubMed1986

Somatomedin C/insulin-like growth factor I: simplified purification procedure and biological activities of the purified growth factor.

Human somatomedin C has been purified from Cohn fraction IV paste by a simplified procedure using chromatofocusing, hydroxylapatite chromatography and reverse-phase high performance chromatography. The purified material has a specific activity by somatomedin C radioimmunoassay of 9160 units/mg (1 unit is defined as the amount of somatomedin present in 1 ml normal adult male human serum), representing a 650,000-fold purification, and possesses sulphation, mitogenic and insulin-like activities (specific activities of 3388 units/mg, 832 units insulin equivalents/mg and 1122 units/mg respectively). Somatomedin C is shown to be a potent stimulator of DNA synthesis (50% maximum stimulation at 150 fmol/ml) in isolated chondrocytes derived from costal cartilage, a major physiological target tissue.

Amino Acids↗
PubMed1986

Similarities between the insulin-like stimulatory effect of human IgG and NSILP.

Since the insulin-like stimulatory effect of human IgG on adipocyte lipogenesis, exerted through its Fc moiety, is not neutralized by anti-insulin antisera, IgG may contribute significantly to the non-suppressible insulin-like activity (NSILA) of plasma. 91% of NSILA has been shown previously to be associated with a high mol. wt. protein (NSILP). The purpose of this investigation was to assess whether IgG and NSILP have similar stimulatory effects on adipocyte lipogenesis and whether this effect can be neutralized by preincubation with gamma-chain specific anti-IgG antiserum; whether IgG stimulates 35S-sulphate uptake by porcine cartilage, known to be stimulated by insulin-like growth factors but not NSILP; and whether gamma-chain specific anti-IgG antisera precipitate IgG in a fashion similar to that with IgG preparations. Our investigations show that both IgG and NSILP have similar dose response relationships with respect to the stimulation of adipocyte lipogenesis and that both lose their adipocyte stimulating effect following preincubation with anti-IgG antiserum; neither IgG nor NSILP stimulate 35S-sulphate uptake by porcine cartilage, unlike serum somatomedin and crude NSILA-s preparations; and that gamma-chain specific anti-IgG antisera form precipitin lines with NSILP. Therefore, NSILP and IgG molecules have immunological and biological similarities; there may occur a homology between the Fc fragment of IgG and the NSILP molecule.

Adipose Tissue↗
PubMed1985

Axon terminals of the projection from the superior colliculus to the olivary pretectal nucleus in the rat.

The terminals of axons projecting to the olivary pretectal nucleus have been identified by electron microscopy following injections of horseradish peroxidase into the superior colliculus of adult albino rats. The labelled terminals were equated with RD-terminals described in previous studies of this nucleus. They were 0.3-1.3 micron in diameter and contained round synaptic vesicles. Most also contained small dark mitochondria. They established Gray type 1 synaptic contacts with the dendrites of presumptive projection cells. Most terminated within non-glomerular neuropil, chiefly in the peripheral 'shell' of the nucleus; a few terminated in regions of glomerular neuropil.

Animals↗
PubMed1985

Unscheduled DNA synthesis induced by streptonigrin in ataxia telangiectasia fibroblasts.

Streptonigrin is an antitumour antibiotic, which at low doses produces DNA strand breaks in cultured cells leading, e.g., to decreased colony-forming ability and decreased rates of DNA synthesis. At higher doses the drug can induce unscheduled DNA synthesis (UDS) presumably as a consequence of excision of large DNA adducts. Ataxia telangiectasia (A-T) cells are unusually sensitive to streptonigrin, but we show here that they can perform excision repair, as demonstrated by UDS, at the same level as normal cells following exposure to the drug. This result suggests that of the apparent two modes of action of streptonigrin it is the DNA strand-breaking capacity to which A-T cells are unusually sensitive. This is consistent with previous reports suggesting some form of DNA strand break in A-T cells is deficiently repaired.

Ataxia Telangiectasia↗
PubMed1985

Effects of ionizing radiation on cells from Fanconi's anemia patients.

The lymphocytes from some Fanconi's anemia patients appeared to be more radiosensitive than normal as measured by the number of X-ray-(or bleomycin-) induced chromosome aberrations seen following G2 treatment. Fibroblasts from the same patients, however, all showed the same degree of colony survival as normals following exposure to gamma-rays [Do, 1.13 +/- 0.072 (S.E.) Gy and 1.14 +/- 0.077 Gy for Fanconi's anemia and normal fibroblasts, respectively]. The lack of increased radiosensitivity in Fanconi's fibroblasts was also observed by the same degree of inhibition of DNA synthesis as seen in normals following gamma-irradiation. The results show clearly that there is no increase in radiosensitivity common to all cell types from Fanconi's patients, although an apparent increase in chromosomal radiosensitivity may be seen in the lymphocytes from an occasional patient.

Adult↗
PubMed1985

In vitro cultivation of Trypanosoma congolense: establishment of infective mammalian forms in continuous culture after isolation from the blood of infected mice.

Bloodstream form trypomastigotes of four cloned stocks of Trypanosoma congolense from West Africa were successfully adapted to continuous in vitro culture at 28 degrees C using bovine aorta endothelial cell monolayers and Eagle's minimum essential medium supplemented with 20% normal bovine serum or foetal calf serum. The trypanosomes maintained in vitro morphologically resembled bloodstream forms and remained infective for vertebrate hosts. They also induced local skin reactions in rabbits and were therefore designated "mammalian forms", possibly resembling parasites which develop extravascularly in the vertebrate host following introduction of metacyclic trypanosomes into the skin by bites of tsetse flies. Mammalian forms of two stocks were allowed to transform to procyclic trypanosomes in order to obtain cultures producing epimastigote and metacyclic stages of T. congolense. Metacyclic trypanosomes produced in this manner were shown to be neutralized by antiserum raised in rabbits against the homologous trypanosome stock transmitted by tsetse flies.

Animals↗
PubMed1985

In vitro cultivation of Trypanosoma congolense: the production of infective forms from metacyclic trypanosomes cultured on bovine endothelial cell monolayers.

After transfer to bovine endothelial cell monolayers cultured in Eagle's minimal essential medium at 28 degrees C or 37 degrees C metacyclic trypanosomes of three cloned stocks of Trypanosoma congolense became morphologically similar to parasites found in the bloodstream of the vertebrate host. The trypanosomes resumed division and grew in close association with the mammalian cells, which were essential for growth. These dividing infective forms had the ability to cause local skin reactions and systemic infections when inoculated intradermally into rabbits. Trypanosomes grown in medium supplemented with foetal calf serum (FCS) eventually differentiated into procyclic forms. No such change occurred in medium supplemented with normal bovine serum. If procyclic forms in FCS were allowed to continue their differentiation at 28 degrees C they eventually produced epimastigotes which gave rise to infective metacyclic trypanosomes once more. It was thus possible to grow and maintain several different developmental stages of T. congolense by varying culture conditions.

Animals↗
PubMed1984

Clinical and cytogenetic diversity in Fanconi's anaemia.

Abnormally high levels of spontaneous and mitomycin C or diepoxybutane induced chromosome breakage were observed in lymphocytes from eight out of nine previously undescribed patients clinically diagnosed as having Fanconi's anaemia. The results suggest that the combination of spontaneous and induced chromosome breakage is a good aid in the differential diagnosis and we suggest that increased chromosome breakage is pathognomonic for this recessive disorder. It is, however, not possible to demonstrate consistently raised levels of induced chromosome breakage in obligate carriers. The patient who had normal levels of chromosome breakage had an atypical haematological picture and may suffer from a disease genetically different from Fanconi's anaemia.

Adolescent↗