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Biomedical subjects

D S Taylor

Publications and source records attributed to D S Taylor.

At least 73 records · Page 4Linked to original sources
PubMed1989

The effect of streptozotocin-induced diabetes on phenylalanine hydroxylase expression in rat liver.

The impact of experimentally induced diabetes on the expression of rat liver phenylalanine hydroxylase has been investigated. A significant elevation in maximal enzymic activity was observed in diabetes. This was associated with significant increases in the amount of enzyme, the phenylalanine hydroxylase-specific translational activity of hepatic RNA and the abundance of phenylalanine hydroxylase-specific mRNA. These changes in phenylalanine hydroxylase expression were not observed when diabetes was controlled by daily injections of insulin. These results are discussed in relation to the hormonal control of phenylalanine hydroxylase gene expression.

Animals↗
PubMed1989

Monoclonal antibodies directed against basic fibroblast growth factor which inhibit its biological activity in vitro and in vivo.

A panel of four murine monoclonal IgG1 antibodies (mAbs) to a recombinant form of basic fibroblast growth factor (bFGF) was produced using somatic cell fusion techniques. Non-linear regression analysis of radioimmunoassay data for each mAb yielded the following dissociation constants (nM) for their interactions with bFGF: DE6 (0.822); AF11 (2.0); FE8 (2.31); and DG2 (20.0). One of the mAbs, DG2, was identified as a bFGF neutralizing antibody on the basis of its ability to inhibit, in vitro, the binding of [125I]-bFGF to high and low affinity bFGF sites on cultured baby hamster kidney cells and bFGF-induced [3H]-thymidine incorporation in cultured 3T3 cells, and in vivo, the angiogenic response to bFGF in a rat kidney capsule model of angiogenesis. The other mAbs displayed varying inhibitory activities in these assays. These mAbs, particularly DG2, may be well suited for a number of applications in bFGF research including immunoassays, immunohistochemical studies, and as functional antagonists of bFGF for examining its role in physiological processes such as reproduction, growth, and development.

Animals↗
PubMed1989

Binding of tissue plasminogen activator to cultured human fibroblasts.

The binding of 125I-labeled, one-chain tissue plasminogen activator (t-PA) by WI-38 cultured human lung fibroblasts was investigated. Binding of t-PA to WI-38 monolayers was specific, saturable and temperature dependent. One and two-chain t-PAs were comparable in their ability to compete with 125I-labeled, one-chain t-PA for binding to fibroblasts, while no inhibition of binding was observed with a 500-fold molar excess of urokinase. Studies with various compounds suggest that neither the catalytic site, the fibrin binding site, nor the carbohydrate moieties on t-PA are involved in its binding to WI-38 cells. At higher temperatures, the amount of cell-bound 125I-t-PA that was removed by either incubation in binding buffer containing an excess of unlabeled t-PA, or by brief treatment with acidic buffer, was small (approximately 20%) suggesting that much of the t-PA is internalized. Electrophoretic analysis of extracts prepared from cells that had been incubated with 125I-t-PA revealed the presence of a major band of 70,000 Mr, which corresponds to intact t-PA. Our results suggest that WI-38 fibroblasts are capable of binding and internalizing t-PA, and that these processes involve a receptor site specific for t-PA.

Binding, Competitive↗
PubMed1989

The electroretinogram.

The electroretinogram, findings, in response to a flash stimulus, was recorded from a skin electrode placed on the bridge of the nose in 4465 infants and children seen over a 10 year period. The electroretinogram was combined with a flash visual evoked potential. From this total, the electroretinographic findings in 240 patients, aged 1 day to 17 years, without suspected retinal pathology and with a normal visual evoked potential, were used as controls and normal electroretinographic parameters of different age groups defined. There were 332 patients who showed an absent or very reduced amplitude electroretinogram. They were divided into primarily ocular disorders (n = 195), neurodegenerative disorders (n = 94), and various syndromes (n = 43). Fundus examination did not always show any obvious abnormalities. The use of this simple and reliable technique for recording the electroretinogram made it possible to include this investigation as a routine procedure without the need for sedation in infants and uncooperative children. Electroretinographic studies, especially when combined with visual evoked potentials, and in some cases electroencephalography, may aid diagnosis in a wide variety of paediatric conditions, many of which have genetic implications.

Adolescent↗
PubMed1989

Leber's congenital amaurosis--a new syndrome with a cardiomyopathy.

Seven members of four families had nystagmus noted by 4 months of age, poor vision, photophobia, and a markedly reduced or absent electroretinogram. Six of these patients had a life threatening episode of cardiac failure in infancy. There were also two neonatal deaths, and one of the affected children died at 2 years and one at 19 years. The five surviving children are well, remain with nystagmus, and have visual acuities of less than 6/60, with the eldest two having lost perception of light. They have a short obese habitus distinct from that of their unaffected siblings and parents.

Blindness↗
PubMed1988

The infant corneal endothelium.

Specular microscopy of the in vivo corneal endothelium of 48 clinically normal eyes of 31 infants less than 1 year old revealed a regular mosaic of small cells. The cell population density of individuals varied greatly, as it does in age-related adults. Reexamination of five eyes indicated a reduction of the cell population density during the first year. This change could be accounted for by corneal growth in the absence of endothelial mitoses and not necessarily by true cell loss. There were morphologic indications of mitoses, but their interpretation is open to doubt.

Endothelium, Corneal↗
PubMed1988

Recovery after optic neuritis in childhood.

Thirty-nine children who presented with optic neuritis in childhood were reviewed after a follow up period from 3 months to 29 years (mean 8.8 years). At follow-up, 30 out of 39 (77%) of the children had had no further episodes and in three (8%) there was recurrence of optic neuritis alone. Multiple sclerosis had developed in six patients (15%), a much lower frequency than after optic neuritis in adult life. Regardless of the initial degree of visual impairment or neurological outcome, the visual prognosis was excellent. Pattern evoked potentials at follow-up were much more frequently normal (55%) than in adults (10%) after optic neuritis.

Adolescent↗
PubMed1988

Cortical somatosensory-evoked potentials in the horse.

Cortical somatosensory-evoked potentials (SEP) were recorded from thoracic and pelvic limbs in 15 horses (13 Thoroughbreds and 2 Quarter Horses). Ulnar nerve SEP were evoked by electrical stimulation of the lateral palmar branch of the ulnar nerve at the level of the metacarpophalangeal joint. Recordings were taken between electrodes at 2 cm lateral to the vertex (contralateral to the stimulated limb) and the midpoint of the interorbital line. Four peaks were found in all recordings: N1, P1, N2, and P2. Latencies to the peaks were 39.0 +/- 2.7, 45.5 +/- 5.3, 50.4 +/- 5.2, and 62.3 +/- 3.7 ms (mean +/- SD), respectively. Tibial nerve SEP were evoked by stimulation of the lateral plantar nerve branch of the tibial nerve at the level of the metatarsophalangeal joint. Recordings were taken between electrodes at the vertex (contralateral to the stimulated limb) and the midpoint of the interorbital line. Four peaks were also found in all tibial nerve SEP recordings: N1, P1, N2, and P2. Latencies to the peaks were 64.6 +/- 11.8, 84.5 +/- 9.7, 121.2 +/- 11.6, and 134.0 +/- 11.1 ms, respectively. Amplitude variability was high for the ulnar nerve and the tibial nerve SEP. There was no effect of sex seen on peak latency or amplitude, and peak latencies were not affected by body length.

Animals↗
PubMed1987

Anti-HLA class I antibodies inhibit the T cell-independent proliferation of human B lymphocytes.

The role of major histocompatibility complex-encoded class I molecules in the proliferation of human B lymphocytes is presently unclear. This question was addressed by investigating the effect of three individually derived anti-HLA class I monoclonal antibodies (mAb) on purified human B cells (less than 1.5% T cells) stimulated by either the T-independent mitogen Staphylococcus aureus or the phorbol ester, phorbol-12-myristate-13-acetate. The three anti-HLA class I antibodies, whether specific for gene products of the HLA-A locus (mAb 131), HLA-B locus (mAb 4E), or HLA-A, -B, and -C locus (mAb W6/32), inhibited S. aureus-induced proliferation by 70 to 90%. This inhibition was significant over a 5-day culture period, was not altered by the addition of exogenous interleukin 2 or B cell growth factor, and was not due to nonspecific cytotoxicity. In addition, the inhibition of proliferation was unchanged when the mAb were added 12 hr after the initiation of culture. The proliferative response was not affected by either of the control antibodies OKB7 and R3-367. In contrast with S. aureus-stimulated B cells, phorbol-12-myristate-13-acetate-induced proliferation was resistant to the inhibitory activity of HLA class I-specific antibodies. These results suggest that HLA class I molecules are involved in human B lymphocyte proliferation and may regulate a critical event preceding the upregulation of protein kinase C activity.

Antibodies, Monoclonal↗
PubMed1986

IL 2 alone is mitogenic only for Tac-positive lymphocytes in human peripheral blood.

To investigate the ability of interleukin 2 (IL 2) alone to induce proliferation of resting human lymphocytes, we stimulated human peripheral blood mononuclear cells (PBMC) with an immunopurified preparation of IL 2 or with phytohemagglutinin (PHA). Proliferation and the percent of cells expressing IL 2 receptors were assessed over 6 days of culture. Regardless of the stimulus, the percent of cells bearing an IL 2 receptor paralleled the amount of proliferation, and proliferation was inhibited by an anti-IL 2 receptor monoclonal antibody (anti-Tac). When stimulated by IL 2 alone, less than 8% of PBMC expressed an IL 2 receptor after 24 hr of culture. Stimulation by IL 2 caused both proliferation and IL 2 receptor expression to increase over the entire culture period (routinely to 75,000 cpm and 50% respectively). When colchicine was added (to inhibit cell division), the percent of cells bearing an IL 2 receptor did not increase. IL 2 alone also induced proliferation of PBMC depleted of accessory cells, with the same kinetics but reduced peak response. Both accessory cells and supernatants that showed IL 1 but not IL 2 activity augmented this proliferation 50 to 100%. In contrast to the effect of IL 2, 25 to 50% of PBMC stimulated by PHA expressed an IL 2 receptor after 24 hr of culture. PHA-induced proliferation and IL 2 receptor expression peaked early in the culture period (routinely to 100,000 cpm and 50% respectively within 3 days), and colchicine did not inhibit the early induction of IL 2 receptors on PBMC. Our findings indicate that unlike PHA, IL 2 induces proliferation of PBMC (or PBMC depleted of accessory cells) by expanding the small percentage of cells in a resting population that already express IL 2 receptors. IL 2 does not appear to induce IL 2 receptors on cells previously lacking this molecule. We also find that IL 1 can enhance the response to IL 2 alone.

Antigen-Presenting Cells↗
PubMed1986

Functional role of HLA class I cell-surface molecules in human T-lymphocyte activation and proliferation.

This investigation addressed the role of major histocompatibility complex-encoded class I molecules in the activation and proliferation of human lymphocytes. We studied the effect of antibodies specific for HLA-A and HLA-B locus gene products on mitogen-stimulated peripheral blood mononuclear cell (PBMC) subpopulations. Three individually derived, well-characterized anti-HLA class I monoclonal antibodies were demonstrated to inhibit the proliferation of human PBMC stimulated by either OKT3 or the calcium ionophore ionomycin. The antibody directed against HLA-A, -B, and -C locus gene products (W6/32) and the antibody directed against HLA-B locus gene products (4E) inhibited proliferation induced by either mitogen by 70-90%. The HLA-A locus-specific antibody (131), though inhibiting ionomycin-induced proliferation by 80-90%, was much less effective when OKT3 was the stimulus. The inhibition affected T4+ and T8+ cells and was not mediated by DR+ accessory cells. The inhibitory effect of these antibodies was associated with a decrease in the level of interleukin 2 activity present in culture supernatants, decreased interleukin 2 receptor expression, and decreased transferrin receptor expression and was not overcome by the addition of exogenous interleukin 2. Our results suggest that HLA class I molecules are directly involved in the early critical events of human lymphocyte activation and proliferation.

Antibodies, Monoclonal↗
PubMed1985

Cyclosporin A directly inhibits human B-cell proliferation by more than a single mechanism.

Cyclosporin A (CsA) is a potent immunosuppressive agent that inhibits T-cell proliferation and lymphokine production. There is less information on the direct effect of CsA on B-cells. We investigated the proliferative responses of human tonsillar B-lymphocytes to a "T dependent" mitogen, pokeweed mitogen (PWM), and to a "T independent" mitogen, Staphylococcus aureus (SA). Both responses were strongly inhibited by CsA. Nonspecific cytotoxicity was ruled out, and the inhibition was not reversed by adding IL1, IL2, or BCGF individually or in combination. Maximal inhibition of the PWM response occurred when CsA was added early in the culture period. Cyclosporin A added 18 hours after the start of culture was less effective, and adding CsA after 36 hours resulted in only minimal inhibition. However, with SA as mitogen, addition after 36 hours still affected substantial inhibition. These results, on the time of action and resistance to reversal by exogenous growth factors, suggest that CsA can directly inhibit human B-cells by a mechanism similar to its action on T-lymphocytes, blocking an early event critical to entry into cell cycle, but an additional mechanism of inhibition later in the cell cycle may also operate when the proliferative signal is provided by the T-independent mitogen SA.

B-Lymphocytes↗
PubMed1985

Histiocytosis X: an ophthalmological review.

Of 76 children with histiocytosis X 18 had orbital involvement, and four developed additional neuro-ophthalmic complications. No instance of intraocular involvement was detected. Among those patients with ophthalmic involvement the main problems were bilateral or unilateral proptosis, ptosis, papilloedema, optic atrophy, and seventh nerve palsy. Only one patient developed a severe visual defect. Management of the ophthalmological complications depends not only on the extent of the orbital disease but also on the degree of systemic involvement. Overall management by a paediatric oncologist is mandatory.

Child↗
PubMed1985

Bilateral macular dysplasia ('colobomata') and congenital retinal dystrophy.

Three unrelated patients with bilateral macular dysplasia ('colobomata') with no relevant family history were found to have absent or substantially abnormal electroretinograms, implying that there was an associated retinal dystrophy. This may suggest that the macular lesions are associated with a global failure of retinal development, with a regional preponderance rather than a purely localised cause such as an intrauterine infection. It is important to distinguish between congenital infections such as toxoplasmosis and developmental macular colobomata, which have a somewhat similar ophthalmoscopic appearance as a cause of bilateral macular abnormalities seen in young children, since they have different implications for genetic advice and future ophthalmic care.

Adolescent↗
PubMed1985

Stimulation and inhibition of human T cell subsets by wheat germ agglutinin.

Wheat germ agglutinin (WGA), a tetravalent lectin, has both stimulatory and inhibitory effects on human T lymphocytes. It has been suggested that these actions are related and that WGA selectively stimulates a suppressive subset of T cells. We studied the ability of WGA to stimulate and inhibit subpopulations of human peripheral blood mononuclear cells (PBMC) known to have helper or suppressor activity. Fresh human PBMC were depleted of either T4+ or T8+ cells by using antibody-mediated complement lysis. The resultant cell populations were stimulated with WGA, and the proliferative response was assessed by [3H]thymidine incorporation, IL 2 receptor expression, the ability to elaborate IL 2 in culture supernatants, and the susceptibility to inhibition by the monoclonal antibody anti-Tac. Similar experiments with cells from a WGA-responsive continuous T cell culture were also performed. WGA inhibited phytohemagglutinin (PHA)-induced proliferation of PBMC depleted of either T4+ or T8+ cells. WGA also inhibited PBMC that had been depleted of adherent cells and Ia+ cells and then induced to proliferate with a combination of TPA and PHA. Our findings indicate that WGA induces IL 2-dependent proliferation in a small proportion of both T4+ and T8+ lymphocytes. We also provide evidence that the inhibitory activity of WGA is not mediated by a T4+, T8+, or Ia+ cell, suggesting that WGA acts directly on the proliferating cell rather than selectively stimulating a suppressive subpopulation.

Dose-Response Relationship, Immunologic↗